Choi Jerome J, Koscik Rebecca L, Jonaitis Erin M, Panyard Daniel J, Morrow Autumn R, Johnson Sterling C, Engelman Corinne D, Schmitz Lauren L
Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53726, USA.
Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53726, USA.
Metabolites. 2023 Nov 16;13(11):1154. doi: 10.3390/metabo13111154.
(1) Smoking is the most significant preventable health hazard in the modern world. It increases the risk of vascular problems, which are also risk factors for dementia. In addition, toxins in cigarettes increase oxidative stress and inflammation, which have both been linked to the development of Alzheimer's disease and related dementias (ADRD). This study identified potential mechanisms of the smoking-cognitive function relationship using metabolomics data from the longitudinal Wisconsin Registry for Alzheimer's Prevention (WRAP). (2) 1266 WRAP participants were included to assess the association between smoking status and four cognitive composite scores. Next, untargeted metabolomic data were used to assess the relationships between smoking and metabolites. Metabolites significantly associated with smoking were then tested for association with cognitive composite scores. Total effect models and mediation models were used to explore the role of metabolites in smoking-cognitive function pathways. (3) Plasma N-acetylneuraminate was associated with smoking status Preclinical Alzheimer Cognitive Composite 3 (PACC3) and Immediate Learning (IMM). N-acetylneuraminate mediated 12% of the smoking-PACC3 relationship and 13% of the smoking-IMM relationship. (4) These findings provide links between previous studies that can enhance our understanding of potential biological pathways between smoking and cognitive function.
(1) 吸烟是现代世界中最主要的可预防健康危害因素。它会增加血管问题的风险，而血管问题也是痴呆症的风险因素。此外，香烟中的毒素会增加氧化应激和炎症，这两者都与阿尔茨海默病及相关痴呆症（ADRD）的发展有关。本研究利用来自威斯康星州阿尔茨海默病预防纵向登记处（WRAP）的代谢组学数据，确定了吸烟与认知功能关系的潜在机制。(2) 纳入了1266名WRAP参与者，以评估吸烟状况与四个认知综合评分之间的关联。接下来，使用非靶向代谢组学数据评估吸烟与代谢物之间的关系。然后测试与吸烟显著相关的代谢物与认知综合评分之间的关联。使用总效应模型和中介模型来探索代谢物在吸烟 - 认知功能途径中的作用。(3) 血浆N - 乙酰神经氨酸与吸烟状况、临床前阿尔茨海默病认知综合评分3（PACC3）和即时学习（IMM）相关。N - 乙酰神经氨酸介导了吸烟与PACC3关系的12%以及吸烟与IMM关系的13%。(4) 这些发现为之前的研究建立了联系，能够增强我们对吸烟与认知功能之间潜在生物学途径的理解。
