Abstract：
Studies of self-reported coffee consumption and smoking on risk of dementia have shown results conflicting with two-sample Mendelian randomization studies. We tested the hypotheses that coffee consumption and smoking influence risk of dementia using observational and one-sample Mendelian randomization designs with individual level data.
We included 114,551 individuals from two Danish general population cohorts (median age 58 years). First, we tested whether high self-reported coffee consumption/smoking were associated with risk of dementia. Second, whether genetically predicted high coffee consumption/smoking due to variation near CYP1A1/AHR/CHRNA3 genes were associated with risk of dementia.
We observed 3,784 dementia events. Moderate self-reported coffee consumption was associated with low risk of all dementia and non-Alzheimer\'s dementia, with a similar trend for Alzheimer\'s disease. Genetically predicted high coffee consumption was associated with high risk of all dementia (hazard ratio [95% confidence interval] per +1 cup/day: 1.20 [1.01-1.42]), with a similar trend for non-Alzheimer\'s dementia (1.23 [0.95-1.53]). High self-reported smoking was associated with high risk of non-Alzheimer\'s dementia. High genetically predicted smoking was associated with a trend towards high risk of all dementia and Alzheimer\'s disease (hazard ratios per +1 pack-year: 1.04 [0.96-1.11]) and 1.06 [0.97-1.16]).
Moderate self-reported coffee consumption was associated with low risk of all and non-Alzheimer\'s dementia, while high genetically predicted coffee consumption was associated with a trend towards the opposite. High self-reported smoking was associated with high risk of non-Alzheimer\'s dementia, with a similar trend for genetically predicted smoking on all dementia and Alzheimer\'s disease.
We included 114,551 individuals from two Danish general population cohorts (median age 58 years). First, we tested whether high self-reported coffee consumption/smoking were associated with risk of dementia. Second, whether genetically predicted high coffee consumption/smoking due to variation near CYP1A1/AHR/CHRNA3 genes were associated with risk of dementia.
We observed 3,784 dementia events. Moderate self-reported coffee consumption was associated with low risk of all dementia and non-Alzheimer\'s dementia, with a similar trend for Alzheimer\'s disease. Genetically predicted high coffee consumption was associated with high risk of all dementia (hazard ratio [95% confidence interval] per +1 cup/day: 1.20 [1.01-1.42]), with a similar trend for non-Alzheimer\'s dementia (1.23 [0.95-1.53]). High self-reported smoking was associated with high risk of non-Alzheimer\'s dementia. High genetically predicted smoking was associated with a trend towards high risk of all dementia and Alzheimer\'s disease (hazard ratios per +1 pack-year: 1.04 [0.96-1.11]) and 1.06 [0.97-1.16]).
Moderate self-reported coffee consumption was associated with low risk of all and non-Alzheimer\'s dementia, while high genetically predicted coffee consumption was associated with a trend towards the opposite. High self-reported smoking was associated with high risk of non-Alzheimer\'s dementia, with a similar trend for genetically predicted smoking on all dementia and Alzheimer\'s disease.
摘要：
关于自我报告的咖啡消费和吸烟对痴呆症风险的研究表明，结果与孟德尔随机两项样本研究相冲突。我们使用观察性和单样本孟德尔随机化设计与个体水平数据检验了咖啡消费和吸烟影响痴呆风险的假设。
我们纳入了来自两个丹麦普通人群队列（中位年龄58岁）的114,551名个体。首先,我们测试了自我报告的高咖啡摄入量/吸烟是否与痴呆风险相关.第二,基因预测CYP1A1/AHR/CHRNA3基因附近变异导致的高咖啡消费/吸烟是否与痴呆风险相关.
我们观察到3,784例痴呆事件。适度的自我报告的咖啡消费与所有痴呆和非阿尔茨海默痴呆的低风险相关。与阿尔茨海默病的趋势相似。遗传预测的高咖啡摄入量与所有痴呆症的高风险相关（每+1杯/天的风险比[95%置信区间]：1.20[1.01-1.42]），非阿尔茨海默氏症的趋势相似（1.23[0.95-1.53]）。高自我报告吸烟与非阿尔茨海默痴呆的高风险相关。高基因预测吸烟与所有痴呆和阿尔茨海默病的高风险趋势相关(每+1包年的风险比:1.04[0.96-1.11])和1.06[0.97-1.16])。
适度的自我报告的咖啡消费与所有和非阿尔茨海默氏症痴呆的低风险相关，而高基因预测的咖啡消费量与相反的趋势有关。高自我报告吸烟与非阿尔茨海默氏症痴呆的高风险相关，与遗传预测吸烟对所有痴呆和阿尔茨海默病的趋势相似。
我们纳入了来自两个丹麦普通人群队列（中位年龄58岁）的114,551名个体。首先,我们测试了自我报告的高咖啡摄入量/吸烟是否与痴呆风险相关.第二,基因预测CYP1A1/AHR/CHRNA3基因附近变异导致的高咖啡消费/吸烟是否与痴呆风险相关.
我们观察到3,784例痴呆事件。适度的自我报告的咖啡消费与所有痴呆和非阿尔茨海默痴呆的低风险相关。与阿尔茨海默病的趋势相似。遗传预测的高咖啡摄入量与所有痴呆症的高风险相关（每+1杯/天的风险比[95%置信区间]：1.20[1.01-1.42]），非阿尔茨海默氏症的趋势相似（1.23[0.95-1.53]）。高自我报告吸烟与非阿尔茨海默痴呆的高风险相关。高基因预测吸烟与所有痴呆和阿尔茨海默病的高风险趋势相关(每+1包年的风险比:1.04[0.96-1.11])和1.06[0.97-1.16])。
适度的自我报告的咖啡消费与所有和非阿尔茨海默氏症痴呆的低风险相关，而高基因预测的咖啡消费量与相反的趋势有关。高自我报告吸烟与非阿尔茨海默氏症痴呆的高风险相关，与遗传预测吸烟对所有痴呆和阿尔茨海默病的趋势相似。
