Abstract
INTRODUCTION
The impact of early-life tobacco exposure on dementia has remained unknown.
METHODS
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.
RESULTS
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.
DISCUSSION
Early-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.
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This post is Copyright: Jiyong Liu,
Yi Xiao,
Xiaoting Zheng,
Yangfan Cheng,
Sirui Zhang,
Yuanzheng Ma,
Qirui Jiang,
Shichan Wang,
Chunyu Li,
Huifang Shang | May 8, 2024