揮發性有機化合物暴露與失智症風險之相關性：回溯性世代研究

Association between volatile organic compounds exposure and dementia risk: a retrospective cohort study in Taiwan

目標：本研究探討不同揮發性有機化合物（volatile organic compounds, VOCs）（包括苯、甲苯、乙苯、間/對-二甲苯）暴露和失智症發生的相關性。方法：本研究以臺灣人體生物資料庫中60歲以上的參與者作為研究對象，並使用土地利用迴歸模型評估揮發性有機化合物、空氣污染物、道路交通噪音及溫度的年平均暴露。我們基於自填問卷的醫師診斷結果及簡易心智量表（Mini-Mental State Examination, MMSE）低於24分來判斷受試者是否為失智症個案，總共參與人數為4,917人。我們使用Cox proportion hazards regression探討揮發性有機化合物與失智症發生的相關性，估計風險比及95%信賴區間，並調整道路交通噪音、空氣污染物（細懸浮微粒[particulate matter with an aerodynamic equivalent diameter≤2.5μm, PM2.5]及二氧化氮[nitrogen dioxide, NO2]）與年平均高溫，計算校正風險。結果：研究對象的苯、甲苯、乙苯、間/對-二甲苯暴露平均分別為3.91±4.31μg/m3、2.50±0.35μg/m3、2.04±1.20μg/m3及10.27±5.78μg/m3，其平均人年數為3.43±0.91年，失智症發生率為1.06%。調整空氣污染物、道路交通噪音及年均高溫後，甲苯對失智症發生的風險為0.67（95%CI: 0.51-0.90），且在不同年齡分組（≦65歲/＞65歲）有顯著的修飾效應（Pinteraction=0.023）。結論：甲苯在共同暴露中與失智症的發生風險有顯著保護相關，且不同年齡分組顯示存在修飾效應。

Objectives: This study was designed to investigate the dementia risk associated with the exposure of volatile organic compounds (VOCs), including benzene, toluene, ethylbenzene, and m/p-xylene. Methods: Individuals aged 60 and above who had been recruited by Taiwan Biobank were identified for inclusion in this study. We used regression models to evaluate exposures to annual average of VOCs, road traffic noise, air pollutants, and temperature. New cases of dementia were determined based on self-reported questionnaires with a diagnosis by a physician and the Mini-Mental State Examination (MMSE) score of less than 24. A total of 4,917 individuals were included in the analysis. Cox proportion hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (95%CI) of dementia associated with the VOCs after adjusting for traffic noise, air pollutants (particulate matter with an aerodynamic equivalent diameter≤2.5μm[PM2.5] and nitrogen dioxide [NO2]), annual high temperature and other confounding factors. Results: The incidence of dementia was 1.06% after 3.43±0.91 years of follow-up for the exposure to average levels of benzene, toluene, ethylbenzene, and m/p-xylenes for 3.91±4.31μg/m3, 2.50±0.35μg/m3, 2.04±1.20μg/m3, and 10.27±5.78μg/m3, respectively. The adjusted HR of dementia was 0.67 (95%CI: 0.51-0.90) associated with toluene after adjusted for other air pollutants, road traffic noise, and annual high temperature, in the co-exposure model of VOCs. Increased risks were associated with traffic noise of 4.96 dBA (HR=1.62, 95%CI: 1.12-2.03) and annual high temperature of 2.86°C (HR=1.85, 95%CI: 1.41-25 2.43). In effect modification analysis, we found that the risk associated with toluene was significantly modified by age (Aged≦65/>65) (Pinteraction=0.023). Conclusions: This study found that toluene has a significant protective association with dementia and significantly modified by age.