Global, regional, and national burden of headache disorders, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023

1990 - 2023年全球、区域和国家层面头痛疾病负担：2023年全球疾病负担研究的系统分析

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates health loss from migraine, tension-type headache, and medication-overuse headache. This study presents updated results on headache-attributed burden from 1990 to 2023, along with clinical and public health implications. Headache disorders, in particular migraine, continue to be a major global health challenge, emphasising the need for effective management and prevention strategies. Much headache-attributed burden could be averted or eliminated by avoiding overuse of medication (including over-the-counter medication), underscoring the importance of public education.

《2023年全球疾病、伤害和危险因素负担研究》（GBD）对偏头痛、紧张性头痛和药物过量使用性头痛导致的健康损失进行了估算。该研究公布了1990年至2023年头痛所致负担的最新结果，以及相关的临床和公共卫生影响。头痛疾病，尤其是偏头痛，仍然是一项重大的全球性健康挑战，这凸显了制定有效管理和预防策略的必要性。通过避免药物（包括非处方药）的过度使用，很大一部分因头痛所致的负担可以得到避免或消除，这也强调了公众健康教育的重要性。

REF: GBD 2023 Headache Collaborators. Global, regional, and national burden of headache disorders, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet Neurol. 2025;24(12):1005-1015. doi:10.1016/S1474-4422(25)00402-8 PMID: 41240916

Lifetime and 10-year absolute risk of cognitive impairment in relation to amyloid PET severity: a retrospective, longitudinal cohort study

与淀粉样蛋白PET严重程度相关的认知障碍终生和10年绝对风险：一项回顾性纵向队列研究

A key knowledge gap concerns the lifetime risk of developing cognitive impairment among individuals who are cognitively unimpaired with abnormal Alzheimer's disease biomarkers. Our aim was to compute lifetime and 10-year absolute risk of cognitive impairment as a function of continuous amyloid PET. Lifetime and 10-year absolute risk for MCI and dementia among individuals who are currently cognitively unimpaired increase with increasing biological severity of Alzheimer's disease. This information should be important for risk-benefit evaluation of therapeutic interventions in the future. The high lifetime risk in participants with higher centiloid values addresses academic controversies concerning risk of future impairment associated with biomarkers of Alzheimer's disease among individuals who are cognitively unimpaired. Ascertainment and modelling of out-of-study outcomes are necessary for accurate lifetime risk estimates.

一个关键的知识空白在于，认知功能正常但阿尔茨海默病生物标志物异常的个体一生中发生认知障碍的风险情况。我们的目的是根据连续的淀粉样蛋白正电子发射断层扫描（PET）结果计算认知障碍的终生和10年绝对风险。目前认知功能正常的个体发生轻度认知障碍（MCI）和痴呆的终生及10年绝对风险会随着阿尔茨海默病生物学严重程度的增加而升高。这一信息对未来治疗干预措施的风险 - 获益评估具有重要意义。半定量单位（Centiloid）值较高的参与者具有较高的终生风险，这解决了关于认知功能正常个体中与阿尔茨海默病生物标志物相关的未来认知障碍风险的学术争议。为了准确估算终生风险，有必要对研究外的结局进行确定和建模。

REF: Jack CR Jr, Hu M, Wiste HJ, et al. Lifetime and 10-year absolute risk of cognitive impairment in relation to amyloid PET severity: a retrospective, longitudinal cohort study. Lancet Neurol. 2025;24(12):1016-1025. doi:10.1016/S1474-4422(25)00350-3 PMID: 41240917

Advances in the genetics and pathology of Lewy body dementia

路易体痴呆遗传学和病理学研究进展

Lewy body dementia is a heterogeneous disease that is underdiagnosed and poorly understood. Pathologically, Lewy body dementia is characterised by the accumulation of intraneuronal aggregates of misfolded α-synuclein, known as Lewy bodies and Lewy neurites. The genetic architecture of Lewy body dementia is complex, involving both common genetic variants with small risk effects and rare genetic variants with large effects. Alzheimer's disease pathology frequently coexists with Lewy body pathology and influences the clinical presentation. A deeper understanding of the pathophysiological pathways, including mitochondrial dysfunction, lysosomal dysfunction, and neuroinflammation, can enhance disease modelling, and this knowledge will ultimately facilitate the development of therapeutic interventions. The biological relationships that Lewy body dementia shares with other neurodegenerative and psychiatric disorders might also be crucial for the development of therapeutic strategies.

路易体痴呆是一种异质性疾病，存在诊断不足且人们对其了解甚少的情况。在病理学上，路易体痴呆的特征是错误折叠的α - 突触核蛋白在神经元内聚集，这些聚集体被称为路易小体和路易神经突。路易体痴呆的遗传结构复杂，既涉及具有小风险效应的常见基因变异，也涉及具有大效应的罕见基因变异。阿尔茨海默病病理经常与路易体病理共存，并影响临床症状表现。更深入地了解包括线粒体功能障碍、溶酶体功能障碍和神经炎症在内的病理生理途径，能够改进疾病模型构建，而这些知识最终将有助于开发治疗干预措施。路易体痴呆与其他神经退行性疾病和精神疾病的生物学联系可能对治疗策略的制定也至关重要。

REF: Scholz SW, Okubadejo NU, Prakash P, Liddelow SA, Ryten M, Halliday GM. Advances in the genetics and pathology of Lewy body dementia. Lancet Neurol. 2025;24(12):1026-1037. doi:10.1016/S1474-4422(25)00363-1 PMID: 41240918

The evolving therapeutic landscape of dementia with Lewy bodies

路易体痴呆不断发展的治疗格局

Dementia with Lewy bodies has a complex clinical presentation, with symptoms spanning cognitive, neuropsychiatric, motor, autonomic, and sleep domains. The disorder causes high morbidity, is associated with high caregiver burden, and can result in considerable health-care costs. Although symptomatic treatments remain scarce, emerging evidence supports a multipronged approach that integrates pharmacological and non-pharmacological interventions that target different signs and symptoms. Novel frameworks, such as the DIAMOND Lewy toolkit, provide structured management guidance. Beyond symptom control, research is at a turning point, with increasing focus on disease-modifying therapies. Ongoing clinical trials are exploring many therapeutic targets, including α-synuclein aggregation and neuroinflammation. Other potential targets in the treatment of dementia with Lewy bodies include amyloid β, given that the presence of Alzheimer's disease copathology is common in patients with this disease.

路易体痴呆临床表现复杂，症状涵盖认知、神经精神、运动、自主神经和睡眠等多个领域。该疾病会导致高发病率，给照顾者带来沉重负担，并可能产生巨额医疗费用。尽管对症治疗方法仍然有限，但越来越多的证据支持采用多维度方法，即整合针对不同体征和症状的药物及非药物干预措施。诸如 DIAMOND 路易体工具包等新型框架，可为管理提供结构化指导。除了控制症状，研究正处于转折点，越来越多的关注集中在疾病修正疗法上。正在进行的临床试验正在探索众多治疗靶点，包括α-突触核蛋白聚集和神经炎症。鉴于阿尔茨海默病共病病理在路易体痴呆患者中较为常见，β-淀粉样蛋白也是治疗路易体痴呆的其他潜在靶点。

REF: Kaila LV, Ikeda M, Sultana J, Chouliaras L, O'Brien JT, Taylor JP. The evolving therapeutic landscape of dementia with Lewy bodies. Lancet Neurol. 2025;24(12):1038-1052. doi:10.1016/S1474-4422(25)00323-0 PMID: 41240919

Diagnostic and other biomarkers of dementia with Lewy bodies: from research to clinical settings

路易体痴呆的诊断及其他生物标志物：从研究到临床应用

Dementia with Lewy bodies is characterised clinically by visual hallucinations, fluctuating cognitive function, parkinsonism, and rapid eye movement sleep behaviour disorder, and can cause more frailty than other dementias. The disease is heterogeneous in presentation and progression, and misdiagnoses are common. In people with dementia with Lewy bodies, other brain copathologies are frequent, limiting the usefulness of some diagnostic biomarkers. This heterogeneity, together with the scarcity of diagnostic and prognostic biomarkers, has hindered the implementation of therapeutic trials. However, novel neuroimaging techniques have emerged with high sensitivity to brain tissue composition and microstructure. Fluid biomarkers are being developed to detect very low concentrations of neuropathological proteins. These biomarkers could soon be adopted in clinical practice and incorporated as outcome measures in clinical trials. These advances will pave the way for early diagnosis, disease monitoring, and prognosis, and will facilitate the implementation of disease-modifying trials.

路易体痴呆在临床上的特征为视觉幻觉、认知功能波动、帕金森综合征和快速眼动睡眠行为障碍，与其他类型痴呆相比，它可能导致患者身体更虚弱。该疾病在临床表现和进展方面具有异质性，误诊情况较为常见。路易体痴呆患者常伴有其他脑部共病，这限制了一些诊断生物标志物的实用性。这种异质性，再加上诊断和预后生物标志物的稀缺，阻碍了治疗试验的开展。然而，新型神经影像学技术应运而生，这些技术对脑组织成分和微观结构具有高敏感性。目前正在开发能够检测极低浓度神经病理蛋白的液体生物标志物。这些生物标志物可能很快会应用于临床实践，并作为临床试验的结局指标。这些进展将为早期诊断、疾病监测和预后评估奠定基础，并有助于开展改变疾病进程的试验。

REF: Zarkali A, Bartl M, Fox NC, Tan LCS, Mollenhauer B, Weil RS. Diagnostic and other biomarkers of dementia with Lewy bodies: from research to clinical settings. Lancet Neurol. 2025;24(12):1053-1065. doi:10.1016/S1474-4422(25)00314-X PMID: 41240920

Blood and CSF biomarkers for multiple sclerosis: emerging clinical applications

多发性硬化症的血液和脑脊液生物标志物：新兴临床应用

Neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (CHI3L1), and other protein assays are being developed as diagnostic or prognostic biomarkers in multiple sclerosis. An increase in NfL concentrations reflects axonal damage resulting from the acute new inflammatory disease activity that occurs during a relapse. NfL concentrations can also reflect the occurrence of new MRI lesions. GFAP concentrations are increased in people with progressive forms of multiple sclerosis, and GFAP is an emerging biomarker of progression independent of relapses. CHI3L1 is an emerging biomarker associated with progression independent of relapse activity and several MRI lesion types, including paramagnetic rim lesions. Some biomarkers, particularly NfL, can help monitoring treatment response, and combinations of multivariate biomarkers provide additional accuracy in specific clinical scenarios. In multiple sclerosis, fluid-based biomarkers are quickly emerging as instruments for clinical monitoring of disease course and patients' response to treatment.

神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）、几丁质酶 - 3 样蛋白 1（CHI3L1）等蛋白检测方法正被开发用作多发性硬化症的诊断或预后生物标志物。NfL 浓度升高反映了复发期间急性新发炎症性疾病活动导致的轴突损伤。NfL 浓度也能反映新发磁共振成像（MRI）病灶的出现。进行性多发性硬化症患者的 GFAP 浓度升高，GFAP 是一种与复发无关的新兴进展性生物标志物。CHI3L1 是一种新兴生物标志物，与不依赖于复发活动的疾病进展以及多种 MRI 病灶类型（包括顺磁性边缘病灶）相关。一些生物标志物，尤其是 NfL，有助于监测治疗反应，多变量生物标志物组合在特定临床场景中能提供更高的准确性。在多发性硬化症中，基于体液的生物标志物正迅速成为临床监测疾病进程和患者治疗反应的工具。

REF: Chitnis T, Magliozzi R, Abdelhak A, Kuhle J, Leppert D, Bielekova B. Blood and CSF biomarkers for multiple sclerosis: emerging clinical applications. Lancet Neurol. 2025;24(12):1066-1078. doi:10.1016/S1474-4422(25)00249-2 PMID: 41015047