Abstract：
BACKGROUND: Long-term exposure to ambient air pollution has been linked with all-cause mortality and cardiovascular and respiratory diseases. Suggestive associations between ambient air pollutants and neurodegeneration have also been reported, but due to the small effect and relatively rare outcomes evidence is yet inconclusive. Our aim was to investigate the associations between long-term air pollution exposure and mortality from neurodegenerative diseases.
METHODS: A Dutch national cohort of 10.8 million adults aged ≥30 years was followed from 2013 until 2019. Annual average concentrations of air pollutants (ultra-fine particles (UFP), nitrogen dioxide (NO2), fine particles (PM2.5 and PM10) and elemental carbon (EC)) were estimated at the home address at baseline, using land-use regression models. The outcome variables were mortality due to amyotrophic lateral sclerosis (ALS), Parkinson\'s disease, non-vascular dementia, Alzheimer\'s disease, and multiple sclerosis (MS). Hazard ratios (HR) were estimated using Cox models, adjusting for individual and area-level socio-economic status covariates.
RESULTS: We had a follow-up of 71 million person-years. The adjusted HRs for non-vascular dementia were significantly increased for NO2 (1.03; 95% confidence interval (CI) 1.02-1.05) and PM2.5 (1.02; 95%CI 1.01-1.03) per interquartile range (IQR; 6.52 and 1.47 μg/m3, respectively). The association with PM2.5 was also positive for ALS (1.02; 95%CI 0.97-1.07). These associations remained positive in sensitivity analyses and two-pollutant models. UFP was not associated with any outcome. No association with air pollution was found for Parkinson\'s disease and MS. Inverse associations were found for Alzheimer\'s disease.
CONCLUSIONS: Our findings, using a cohort of more than 10 million people, provide further support for associations between long-term exposure to air pollutants (PM2.5 and particularly NO2) and mortality of non-vascular dementia. No associations were found for Parkinson and MS and an inverse association was observed for Alzheimer\'s disease.
METHODS: A Dutch national cohort of 10.8 million adults aged ≥30 years was followed from 2013 until 2019. Annual average concentrations of air pollutants (ultra-fine particles (UFP), nitrogen dioxide (NO2), fine particles (PM2.5 and PM10) and elemental carbon (EC)) were estimated at the home address at baseline, using land-use regression models. The outcome variables were mortality due to amyotrophic lateral sclerosis (ALS), Parkinson\'s disease, non-vascular dementia, Alzheimer\'s disease, and multiple sclerosis (MS). Hazard ratios (HR) were estimated using Cox models, adjusting for individual and area-level socio-economic status covariates.
RESULTS: We had a follow-up of 71 million person-years. The adjusted HRs for non-vascular dementia were significantly increased for NO2 (1.03; 95% confidence interval (CI) 1.02-1.05) and PM2.5 (1.02; 95%CI 1.01-1.03) per interquartile range (IQR; 6.52 and 1.47 μg/m3, respectively). The association with PM2.5 was also positive for ALS (1.02; 95%CI 0.97-1.07). These associations remained positive in sensitivity analyses and two-pollutant models. UFP was not associated with any outcome. No association with air pollution was found for Parkinson\'s disease and MS. Inverse associations were found for Alzheimer\'s disease.
CONCLUSIONS: Our findings, using a cohort of more than 10 million people, provide further support for associations between long-term exposure to air pollutants (PM2.5 and particularly NO2) and mortality of non-vascular dementia. No associations were found for Parkinson and MS and an inverse association was observed for Alzheimer\'s disease.
摘要：
背景：长期暴露于环境空气污染与全因死亡率以及心血管和呼吸系统疾病有关。还报道了环境空气污染物与神经变性之间的暗示性关联，但由于效应小和相对罕见的结局，证据还没有定论。我们的目的是调查长期空气污染暴露与神经退行性疾病死亡率之间的关系。
方法：从2013年到2019年，对1,080万年龄≥30岁的成年人进行了调查。空气污染物的年平均浓度(超细颗粒(UFP)，二氧化氮(NO2),细颗粒（PM2.5和PM10）和元素碳（EC）的估计在家庭地址的基线，利用土地利用回归模型。结果变量为肌萎缩侧索硬化症（ALS）导致的死亡率，帕金森病,非血管性痴呆,老年痴呆症,和多发性硬化症（MS）。使用Cox模型估计危险比(HR)，针对个人和地区层面的社会经济地位协变量进行调整。
结果：我们进行了7100万人年的随访。非血管性痴呆的校正HR在每四分位数范围内的NO2（1.03;95％置信区间（CI）1.02-1.05）和PM2.5（1.02;95CI1.01-1.03）（IQR;分别为6.52和1.47μg/m3）显着增加。与PM2.5的相关性也与ALS呈正相关（1.02；95CI0.97-1.07）。在敏感性分析和双污染物模型中，这些关联仍然是积极的。UFP与任何结果无关。帕金森病和MS未发现与空气污染有关。发现了阿尔茨海默病的反向关联。
结论：我们的发现，使用超过1000万人的队列，为长期暴露于空气污染物(PM2.5,特别是NO2)与非血管性痴呆死亡率之间的关联提供进一步支持.未发现帕金森病和MS的相关性，而阿尔茨海默病的相关性呈负相关。
方法：从2013年到2019年，对1,080万年龄≥30岁的成年人进行了调查。空气污染物的年平均浓度(超细颗粒(UFP)，二氧化氮(NO2),细颗粒（PM2.5和PM10）和元素碳（EC）的估计在家庭地址的基线，利用土地利用回归模型。结果变量为肌萎缩侧索硬化症（ALS）导致的死亡率，帕金森病,非血管性痴呆,老年痴呆症,和多发性硬化症（MS）。使用Cox模型估计危险比(HR)，针对个人和地区层面的社会经济地位协变量进行调整。
结果：我们进行了7100万人年的随访。非血管性痴呆的校正HR在每四分位数范围内的NO2（1.03;95％置信区间（CI）1.02-1.05）和PM2.5（1.02;95CI1.01-1.03）（IQR;分别为6.52和1.47μg/m3）显着增加。与PM2.5的相关性也与ALS呈正相关（1.02；95CI0.97-1.07）。在敏感性分析和双污染物模型中，这些关联仍然是积极的。UFP与任何结果无关。帕金森病和MS未发现与空气污染有关。发现了阿尔茨海默病的反向关联。
结论：我们的发现，使用超过1000万人的队列，为长期暴露于空气污染物(PM2.5,特别是NO2)与非血管性痴呆死亡率之间的关联提供进一步支持.未发现帕金森病和MS的相关性，而阿尔茨海默病的相关性呈负相关。
