774 www.thelancet.com/neurology Vol 16 October 2017 Authors’ reply We appreciate the insightful comments pertaining to our Review on the neurological consequences of obesity. Our Review focused on the increasing medical literature supporting an association between obesity and CNS and peripheral nervous system (PNS) injury. Several observational and intervention studies have provided consistent evidence substantiating a potential causal link. The two letters raise important issues pertaining to the strength of the current evidence for other associations involving obesity and CNS outcomes. Jannis Kountouras and colleagues discuss evidence linking Helicobacter pylori infection to metabolic syndrome and neurodegenerative diseases, such as Alzheimer’s disease. Although we acknowledge the evidence referenced by the authors, we think it is important to contrast the amount of evidence implicating H pylori infection in CNS and PNS injury with the evidence supporting the association between obesity and CNS and PNS injury. For H pylori infection, the association with mild cognitive impairment and Alzheimer’s disease is supported by a small number of case-control studies. In contrast, the association between obesity and mild cognitive impairment and Alzheimer’s disease is based on several prospective cohort studies and is further supported by several clinical trials. Similarly, the association between obesity and neuropathy is supported by findings from several cross-sectional studies and is further supported by uncontrolled intervention studies. In summary, inadequate data support the role of H pylori infection in CNS and PNS injury, and further study is required to determine whether this is a promising new area. In contrast, a large body of evidence supports the role of obesity in CNS and PNS injury, which warrants new strategies to determine the best interventions and how to implement them. Ane Mínguez-Olaondo and colleagues highlight the evidence linking obesity with migraine. They reference a meta-analysis of 12 observational studies that revealed an increased risk of migraine in obese people. Migraines are highly prevalent, and current preventative and abortive therapies are only partially effective. Clearly, new interventions are needed and the treatment of obesity is a promising area. The next step should be prospective cohort and intervention studies to further our understanding of the link between obesity and migraine. The report referenced by Minguez-Olaondo and colleagues indicates that the study linking adipokines with migraines uses methods with crucial limitations and that the intervention studies have only been case series. Similarly to the association between obesity and other CNS injury, data supporting an association between obesity and migraine will hopefully continue to increase and lead to new therapeutic interventions. In summary, the evidence supporting an association between obesity and CNS and PNS injury is robust and growing. Further work is needed to enhance our understanding of the mechanistic pathways that link obesity and CNS and PNS injury. Furthermore, we need to determine the best interventions to combat obesity, whether focused on diet, exercise, surgery, or drugs. Perhaps even more importantly, we need to implement the best strategies to reduce obesity and its complications, since a prescription for diet and exercise is easy to write and hard to fulfill.

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肥胖与神经系统：更多问题——作者的回答

774 www.thelancet.com/neurology 第 16 卷 2017 年 10 月 16 日 作者的回复 我们感谢我们对肥胖对神经系统后果的评论所发表的有见地的评论。我们的评论侧重于支持肥胖与 CNS 和周围神经系统 (PNS) 损伤之间关联的越来越多的医学文献。几项观察性和干预性研究提供了一致的证据，证实了潜在的因果关系。这两封信提出了与肥胖和中枢神经系统结果相关的其他关联的当前证据强度有关的重要问题。Jannis Kountouras 及其同事讨论了将幽门螺杆菌感染与代谢综合征和神经退行性疾病（如阿尔茨海默病）联系起来的证据。虽然我们承认作者引用的证据，我们认为将涉及幽门螺杆菌感染的 CNS 和 PNS 损伤的证据数量与支持肥胖与 CNS 和 PNS 损伤之间关联的证据进行对比是很重要的。对于幽门螺杆菌感染，少量病例对照研究支持与轻度认知障碍和阿尔茨海默病的关联。相比之下，肥胖与轻度认知障碍和阿尔茨海默病之间的关联基于多项前瞻性队列研究，并得到多项临床试验的进一步支持。同样，肥胖和神经病变之间的关联得到了几项横断面研究结果的支持，并得到了不受控制的干预研究的进一步支持。总之，没有足够的数据支持幽门螺杆菌感染在 CNS 和 PNS 损伤中的作用，需要进一步研究以确定这是否是一个有前途的新领域。相比之下，大量证据支持肥胖在 CNS 和 PNS 损伤中的作用，这需要新的策略来确定最佳干预措施以及如何实施它们。Ane Mínguez-Olaondo 及其同事强调了肥胖与偏头痛有关的证据。他们参考了一项对 12 项观察性研究的荟萃分析，该研究显示肥胖人群患偏头痛的风险增加。偏头痛非常普遍，目前的预防和中止疗法仅部分有效。显然，需要新的干预措施，肥胖的治疗是一个有前途的领域。下一步应该是前瞻性队列和干预研究，以进一步了解肥胖和偏头痛之间的联系。Minguez-Olaondo 及其同事引用的报告表明，将脂肪因子与偏头痛联系起来的研究使用的方法具有重大局限性，并且干预研究只是病例系列。与肥胖与其他中枢神经系统损伤之间的关联类似，支持肥胖与偏头痛之间关联的数据有望继续增加并导致新的治疗干预措施。总之，支持肥胖与 CNS 和 PNS 损伤之间关联的证据是强有力的并且不断增长。需要进一步的工作来增强我们对将肥胖与 CNS 和 PNS 损伤联系起来的机制途径的理解。此外，我们需要确定对抗肥胖的最佳干预措施，无论是侧重于饮食、运动、手术还是药物。或许更重要的是，