INTRODUCTIONThe impact of early‐life tobacco exposure on dementia has remained unknown.METHODSUsing the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all‐cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease (AD) were analyzed. A Mendelian randomization (MR) analysis was conducted.RESULTSThe time ratios for smokers starting in childhood, adolescence, and adulthood (vs never smokers) were 0.87 (0.76 to 0.99), 0.92 (0.88 to 0.96), and 0.95 (0.89 to 1.01). MSDP and smoking in adolescence altered many brain regions, including the hippocampus. In genetic analysis, MSDP was genetically and causally linked to AD, and a younger ASI was genetically correlated to a higher AD risk.DISCUSSIONEarly‐life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks.Highlights Unlike the commonly used Cox proportional hazards model, this article uses a parametric survival analysis method – the accelerated failure model – to explore the relationship between exposure to onset time. It can be used as an alternative method when the proportional hazards assumption is not met. Genetic analyses including genetic correlation study and MR analysis and brain structure analyses were conducted to support our findings and explore the potential mechanisms. The study reveals the relationship between different smoking initiation periods and the onset time of dementia and shows that earlier smoking exposure has a more significant impact on dementia. It emphasizes the importance of preventing early smoking. In the future, more research focusing on the relationship between early exposure and dementia is called for to provide more detailed prevention measures for dementia that cover all age groups.

中文翻译：

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母亲怀孕期间吸烟和开始吸烟的年龄对痴呆症的影响：一项前瞻性队列研究

简介 生命早期接触烟草对痴呆症的影响仍不清楚。方法使用英国生物银行，通过加速估计母亲怀孕期间吸烟 (MSDP) 和开始吸烟年龄 (ASI) 与全因痴呆发病时间的关系。失效时间模型。分析了MSDP和ASI对大脑结构的影响及其与阿尔茨海默病（AD）的遗传相关性。进行孟德尔随机化 (MR) 分析。 结果 儿童期、青春期和成年期开始吸烟者（与从不吸烟者相比）的时间比分别为 0.87（0.76 至 0.99）、0.92（0.88 至 0.96）和 0.95（0.89 至 1.01） 。 MSDP 和青春期吸烟改变了许多大脑区域，包括海马体。在遗传分析中，MSDP 与 AD 存在遗传和因果关系，而较年轻的 ASI 与较高的 AD 风险具有遗传相关性。讨论 早期吸烟会加速痴呆症的发病，并且与 AD 具有遗传相关性。 MSDP 证明与 AD 风险存在遗传和因果关系。亮点 与常用的Cox比例风险模型不同，本文采用参数生存分析方法——加速失效模型——来探讨暴露与发病时间之间的关系。当不满足比例风险假设时，它可以用作替代方法。 进行了遗传分析，包括遗传相关性研究、磁共振分析和脑结构分析，以支持我们的发现并探索潜在机制。 该研究揭示了不同吸烟起始时期与痴呆症发病时间之间的关系，并表明较早吸烟对痴呆症的影响更为显着。它强调了预防早期吸烟的重要性。未来需要更多关注早期暴露与痴呆之间关系的研究，为覆盖各年龄段的痴呆提供更详细的预防措施。