Department of Neurology, National Clinical Research Center for Geriatric, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, China.
Department of Neurology, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China.
Alzheimers Dement. 2024 Jun;20(6):4066-4079. doi: 10.1002/alz.13854. Epub 2024 May 7.
The impact of early-life tobacco exposure on dementia has remained unknown.
Using 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.
The 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.
Early-life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks.
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.
早年接触烟草对痴呆症的影响尚不清楚。
利用英国生物库，采用加速失效时间模型估计孕期母亲吸烟（MSDP）和开始吸烟年龄（ASI）与全因痴呆症发病时间的关联。分析 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。
儿童期、青春期和成年期开始吸烟（vs 从不吸烟者）的时间比为 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 在遗传上与 AD 相关，并且 ASI 越年轻与 AD 风险越高相关。
早年吸烟加速了痴呆症的发病，并与 AD 具有遗传相关性。MSDP 与 AD 风险具有遗传和因果联系。
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的关系。当不符合比例风险假设时，它可以作为替代方法。进行了遗传分析，包括遗传相关性研究和 MR 分析以及大脑结构分析，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期与痴呆症发病时间的关系，表明早期吸烟暴露对痴呆症的影响更为显著。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症之间关系的研究，为涵盖所有年龄段的痴呆症提供更详细的预防措施。
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