Self-Reported and Genetically Predicted Coffee and Tobacco Consumption in Dementia

Abstract

Background: Studies of self-reported coffee and tobacco consumption on risk of dementia have shown results conflicting with causal genetic studies. We tested the hypotheses that coffee and tobacco consumption causally influence risk of Alzheimer’s disease and non-Alzheimer’s dementia using a Mendelian randomization study design. Methods: We included 114,551 individuals from the general population. First, we tested whether high self-reported coffee and tobacco consumption were associated with risk of dementia. Second, we examined whether two genetic variants near CYP1A1/2 (rs2472297) and AHR (rs4410790) genes were associated with coffee consumption and whether one variant near CHRNA3 was associated with tobacco consumption in our population. Third, we examined whether genetically predicted high coffee and tobacco consumption due to variation in the genetic variants were associated with risk of dementia. Findings: Self-reported coffee and tobacco consumption were not associated with Alzheimer’s disease; however, moderate coffee consumption was associated with low risk and high tobacco consumption was associated with high risk of non-Alzheimer’s dementia. Genetically predicted tobacco and coffee consumption were not associated with risk of Alzheimer’s disease and non-Alzheimer’s dementia: hazard ratios (95% confidence interval) for Alzheimer’s disease and non-Alzheimer’s dementia were 1·16 (0 · 93-1·44) and 1·23 (0·95-1·58) for +1 coffee cup/day and 1·06 (0.97-1·16) and 0·98 (0·88-1·10) for +1 pack-year, respectively. Interpretation: Neither coffee nor tobacco consumption appears to be related convincingly to risk of Alzheimer’s disease or non-Alzheimer’s dementia. Funding: Herlev and Gentofte Hospital, Copenhagen University Hospital. Declaration of Interests: None exist. Ethics Approval Statement: The study was approved by institutional review boards and by Danish ethical committees, and was conducted according to the declaration of Helsinki. Written informed consent was obtained from all individuals included in the study.