Association of Blood Lipoprotein Levels With Incident Alzheimer Disease in Community-Dwelling Individuals: The Framingham Heart Study

社区居民血脂蛋白水平与新发阿尔茨海默病的关联：弗雷明汉心脏研究

Cardiovascular risk factors are important contributors to the risk of Alzheimer disease (AD). To further explore the physiologic links between cardiovascular health and AD risk, we studied the associations between various blood lipoprotein levels and AD risk in community-dwelling older adults. Lower sdLDL-C and higher ApoB48 concentrations were associated with a lower AD risk. In addition, individuals with the lowest HDL-C concentrations were less likely to develop AD compared with the remaining sample. These findings underscore links between lipoprotein metabolism pathways and AD risk, emphasizing the potential role of blood lipoprotein markers in AD risk stratification and of lipid modification strategies in dementia prevention.

心血管危险因素是导致阿尔茨海默病（AD）发病风险的重要因素。为进一步探究心血管健康与AD发病风险之间的生理联系，我们对社区老年人不同血脂蛋白水平与AD发病风险之间的关联进行了研究。较低的小而密低密度脂蛋白胆固醇（sdLDL - C）和较高的载脂蛋白B48（ApoB48）浓度与较低的AD发病风险相关。此外，与其余研究对象相比，高密度脂蛋白胆固醇（HDL - C）浓度最低的个体患AD的可能性更小。这些发现凸显了脂蛋白代谢途径与AD发病风险之间的联系，强调了血液脂蛋白标志物在AD风险分层中的潜在作用，以及脂质调节策略在预防痴呆方面的潜在作用。

REF: Charisis S, Lu S, Melgarejo JD, et al. Association of Blood Lipoprotein Levels With Incident Alzheimer Disease in Community-Dwelling Individuals: The Framingham Heart Study. Neurology. 2025;104(12):e213715. doi:10.1212/WNL.0000000000213715 PMID: 40446198 PMCID: PMC12129701

Estimated Theoretical Benefit of Aggressive LDL Lowering in Patients With Symptomatic Intracranial Atherosclerosis

症状性颅内动脉粥样硬化患者积极降低低密度脂蛋白胆固醇的理论获益估算

Given the high risk of recurrent atherosclerotic vascular events in patients with stroke due to intracranial atherosclerotic disease (ICAD), we estimated the potential benefit of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in this population. Every 10 mg/dL reduction in LDL for patients with stroke due to ICAD is associated with lower rates of recurrent stroke or MI, and this theoretical framework suggests that PCSK9i can help achieve this goal.

鉴于颅内动脉粥样硬化性疾病（ICAD）所致卒中患者发生复发性动脉粥样硬化性血管事件的风险较高，我们评估了前蛋白转化酶枯草溶菌素/kexin 9 型抑制剂（PCSK9i）在这一人群中的潜在获益。ICAD 所致卒中患者的低密度脂蛋白（LDL）每降低 10 mg/dL，复发性卒中和心肌梗死的发生率就会降低，这一理论框架表明 PCSK9i 有助于实现这一目标。

REF: Siegler JE, Badillo Goicoechea E, Yaghi S, et al. Estimated Theoretical Benefit of Aggressive LDL Lowering in Patients With Symptomatic Intracranial Atherosclerosis. Neurology. 2025;105(1):e213768. doi:10.1212/WNL.0000000000213768 PMID: 40446174

Analysis and Prediction of Mortality of Stroke and Its Subtypes Attributable to Particulate Matter Pollution in China From 1990 to 2030

1990 - 2030年中国因颗粒物污染导致的卒中及其亚型死亡情况分析与预测

Stroke remains a major global public health concern, particularly in China, where particulate matter (PM2.5) pollution is a significant contributor to stroke mortality. This study systematically analyzes changes in stroke and subtype-specific mortality attributable to PM2.5 in China from 1990 to 2021 and projects trends up to 2030. China has made significant progress in stroke prevention and air pollution control; however, disparities remain in the effectiveness of prevention across stroke subtypes and population groups. Further efforts should focus on strengthening pollution control, optimizing prevention strategies for each stroke subtype, enhancing hypertension management in middle-aged populations, improving metabolic risk control in older adults, and ensuring efficient health care resource allocation. Priority should be given to high-risk populations, particularly older individuals and men, to address the challenges posed by aging and the increasing burden of chronic diseases.

中风仍然是全球主要的公共卫生问题，在中国尤其如此，细颗粒物（PM2.5）污染是导致中风死亡的重要因素。本研究系统分析了1990年至2021年中国归因于PM2.5的中风及各亚型死亡率的变化，并对至2030年的趋势进行了预测。中国在中风预防和空气污染控制方面取得了显著进展；然而，不同中风亚型和人群的预防效果仍存在差异。未来应进一步加强污染控制，优化各中风亚型的预防策略，加强中年人群的高血压管理，改善老年人的代谢风险控制，并确保卫生保健资源的有效分配。应优先关注高危人群，特别是老年人和男性，以应对人口老龄化和慢性病负担加重带来的挑战。

REF: Cheng Z, Wang J, Xiao C, Liu H, Yu C. Analysis and Prediction of Mortality of Stroke and Its Subtypes Attributable to Particulate Matter Pollution in China From 1990 to 2030. Neurology. 2025;104(12):e213782. doi:10.1212/WNL.0000000000213782 PMID: 40446199

Haemochromatosis Genotypes and Incident Dementia in a Prospective Study of Older Adults

一项针对老年人的前瞻性研究：血色素沉着症基因型与新发痴呆症的关系

Variants in the homeostatic iron regulator (HFE) gene are prevalent among individuals of European ancestry and have been linked to an increased risk of dementia. This study aimed to evaluate the effects of HFE p.Cys282Tyr and p.His63Asp variants on serum ferritin levels and the incidence of dementia in a cohort of initially healthy older adults. Among initially healthy older adults, HFE p.His63Asp homozygosity was associated with a higher risk of incident dementia in men but not women. These findings highlight a potential sex-specific genetic risk factor for dementia and warrant further research into the underlying mechanisms linking p.His63Asp and dementia.

稳态铁调节蛋白（HFE）基因变异在欧洲血统人群中很常见，且与痴呆症风险增加有关。本研究旨在评估HFE基因p.Cys282Tyr和p.His63Asp变异对一组最初健康的老年人血清铁蛋白水平及痴呆症发病率的影响。在最初健康的老年人中，HFE基因p.His63Asp纯合子状态与男性患痴呆症的风险增加有关，但与女性无关。这些发现凸显了痴呆症潜在的性别特异性遗传风险因素，有必要进一步研究p.His63Asp与痴呆症之间的潜在机制。

REF: Yu C, Delatycki M, Hussain SM, McNeil JJ, Lacaze P, Olynyk JK. Haemochromatosis Genotypes and Incident Dementia in a Prospective Study of Older Adults. Neurology. 2025;104(12):e213743. doi:10.1212/WNL.0000000000213743 PMID: 40440589 PMCID: PMC12123751

Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid

未受损的老年人群中，伴和不伴淀粉样蛋白升高者的日常功能变化与tau蛋白和淀粉样蛋白的关联

Everyday functioning declines gradually over time in Alzheimer disease (AD), with the earliest changes potentially occurring at the preclinical stage. We investigated how changes in everyday functioning relate to (changes in) amyloid and tau in a large sample of cognitively unimpaired older adults, most of whom had elevated amyloid levels at the start of the study. Higher tau levels are associated with the fastest decline in everyday functioning in the presence of elevated amyloid, and those accumulating more tau show a faster decline in everyday functioning. These findings demonstrate the utility of including sensitive measures of everyday functioning in clinical practice and clinical trials at the stage of preclinical AD.

在阿尔茨海默病（AD）中，日常功能会随时间逐渐衰退，最早的变化可能出现在临床前期。我们在一大群认知未受损的老年人样本中研究了日常功能的变化与淀粉样蛋白和tau蛋白（及其变化）之间的关系，其中大多数人在研究开始时淀粉样蛋白水平就已升高。在淀粉样蛋白水平升高的情况下，tau蛋白水平越高，日常功能衰退越快，且tau蛋白积累越多的人，日常功能衰退也越快。这些发现表明，在临床前期AD阶段的临床实践和临床试验中纳入对日常功能的敏感测量方法是有用的。

REF: Dubbelman MA, Liu A, Donohue MC, et al. Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. Neurology. 2025;104(12):e213775. doi:10.1212/WNL.0000000000213775 PMID: 40440591 PMCID: PMC12123750

Changes Over 10 Years in Peripheral Nerve Function in People With Well-Controlled Type 2 Diabetes and Those With Normal Glucose Tolerance

血糖控制良好的2型糖尿病患者和糖耐量正常者周围神经功能10年变化情况

There is a lack of knowledge on the changes in peripheral nerve function in people with well-controlled, recently diagnosed type 2 diabetes compared with those with normal glucose tolerance (NGT). In this study, we aimed to investigate the natural course of the function of lower extremity small and large nerve fibers in people with NGT and its decline in those with well-controlled type 2 diabetes. The findings suggest that nerve function deterioration in well-controlled type 2 diabetes is primarily influenced by nerve function status at diagnosis and physiologic aging, rather than diabetes-related progression.

与糖耐量正常（NGT）人群相比，目前缺乏关于血糖控制良好的新诊断2型糖尿病患者周围神经功能变化的相关知识。在本研究中，我们旨在探讨NGT人群下肢小神经纤维和大神经纤维功能的自然变化过程，以及血糖控制良好的2型糖尿病患者神经功能的衰退情况。研究结果表明，血糖控制良好的2型糖尿病患者神经功能恶化主要受诊断时神经功能状态和生理性衰老的影响，而非与糖尿病相关的病情进展。

REF: Strom A, Strassburger K, Ziegler D, et al. Changes Over 10 Years in Peripheral Nerve Function in People With Well-Controlled Type 2 Diabetes and Those With Normal Glucose Tolerance. Neurology. 2025;104(12):e213780. doi:10.1212/WNL.0000000000213780 PMID: 40440593 PMCID: PMC12123752

Association of Self-Reported Sleep Metrics With Imaging Markers of Small Vessel Disease and Cognition in Patients With TIA or Mild Stroke

短暂性脑缺血发作或轻度卒中患者自我报告的睡眠指标与小血管病影像学标志物及认知功能的关联

Disturbed sleep is common after stroke, yet its relationship with cerebral small vessel disease (SVD) and cognitive performance in the stroke population, particularly patients with TIA/mild stroke who are on the milder end of the cerebrovascular spectrum, remains understudied. We aim to examine the associations of self-reported sleep metrics with neuroimaging markers of SVD and cognitive performance in patients with TIA/mild stroke from 2 prospective stroke cohorts. Disturbed sleep, including longer in-bed time and longer sleep duration, was cross-sectionally associated with greater SVD burden and worse cognitive performance in patients with TIA/mild stroke. Future longitudinal studies are warranted to validate our findings.

中风后睡眠障碍很常见，但在中风人群中，尤其是处于脑血管疾病谱系较轻一端的短暂性脑缺血发作（TIA）/轻度中风患者中，睡眠障碍与脑小血管病（SVD）及认知表现之间的关系仍未得到充分研究。我们旨在研究两项前瞻性中风队列中TIA/轻度中风患者自我报告的睡眠指标与SVD神经影像学标志物及认知表现之间的关联。在TIA/轻度中风患者中，睡眠障碍（包括卧床时间更长和睡眠时间更长）与更严重的SVD负担及更差的认知表现存在横断面关联。未来有必要开展纵向研究来验证我们的研究结果。

REF: Liu DX, Ip MS, Lam DC, et al. Association of Self-Reported Sleep Metrics With Imaging Markers of Small Vessel Disease and Cognition in Patients With TIA or Mild Stroke. Neurology. 2025;104(12):e213734. doi:10.1212/WNL.0000000000213734 PMID: 40435444 PMCID: PMC12113490

Use and Eligibility for Glucose-Like Peptide-1 Receptor Agonist Treatment for Primary Prevention of Stroke

胰高血糖素样肽 -1 受体激动剂治疗在卒中一级预防中的应用及适用情况

The 2024 American Heart Association and American Stroke Association stroke prevention guideline newly recommended glucose-like peptide-1 receptor agonists (GLP-1s) for primary prevention of stroke in patients with diabetes and elevated risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to characterize the population newly recommended GLP-1s. Almost 5 million Americans with diabetes would qualify for GLP-1 use for primary prevention of stroke, but current use among this population is very low.

2024年美国心脏协会和美国卒中协会发布的卒中预防指南新推荐，对于患有糖尿病且动脉粥样硬化性心血管疾病（ASCVD）风险升高的患者，可使用胰高血糖素样肽 - 1受体激动剂（GLP - 1类药物）进行卒中一级预防。我们旨在明确新推荐使用GLP - 1类药物的人群特征。近500万美国糖尿病患者符合使用GLP - 1类药物进行卒中一级预防的标准，但该人群目前对这类药物的使用率非常低。

REF: Wilson LM, Anderson TS. Use and Eligibility for Glucose-Like Peptide-1 Receptor Agonist Treatment for Primary Prevention of Stroke. Neurology. 2025;104(12):e213739. doi:10.1212/WNL.0000000000213739 PMID: 40408626 PMCID: PMC12101899

Noninvasive Assessment of the Risk Features of Hemorrhage in Moyamoya Disease Using 7T MRI

使用7T磁共振成像对烟雾病出血风险特征进行无创评估

While digital subtraction angiography (DSA) is traditionally used for moyamoya disease (MMD) assessment, its invasiveness and limitations necessitate alternative methods. The higher signal-to-noise ratio (SNR) and contrast-to-noise ratio of 7T MRI improve the clarity of the image and retains the details of the structures. We aimed to assess the performance of 7T MRI in identifying hemorrhagic risk features of MMD compared with 3T MRI and DSA. The 7T TOF-MRA visualization of dilatation and branching extension of the AChA and PComA indicates a heightened risk of hemorrhage, suggesting that this imaging technique could serve as a valuable noninvasive tool for identifying hemorrhagic vulnerabilities in MMD.

虽然传统上使用数字减影血管造影（DSA）来评估烟雾病（MMD），但其具有侵入性且存在局限性，因此需要其他替代方法。7T磁共振成像（MRI）较高的信噪比（SNR）和对比噪声比可提高图像清晰度并保留结构细节。我们旨在评估7T MRI在识别MMD出血风险特征方面的性能，并与3T MRI和DSA进行比较。7T时间飞跃法磁共振血管造影（TOF - MRA）对脉络膜前动脉（AChA）和后交通动脉（PComA）扩张及分支延伸的显影提示出血风险增加，这表明该成像技术可作为识别MMD出血易感性的一种有价值的非侵入性工具。

REF: Duan Q, Lyu J, Liu Z, et al. Noninvasive Assessment of the Risk Features of Hemorrhage in Moyamoya Disease Using 7T MRI. Neurology. 2025;104(11):e213617. doi:10.1212/WNL.0000000000213617 PMID: 40397837 PMCID: PMC12096881