Background

Although there is increasing evidence that environmental exposures are associated with the risk of neurodegenerative conditions, there is still limited mechanistic evidence evaluating potential mediators in human populations.

Methods

UK Biobank is a large long-term study of 500,000 adults enrolled from 2006 to 2010 age 40–69 years. ICD-10 classified reports of dementia cases up to 2022 (Alzheimer’s disease, vascular dementia, dementia in other classified diseases, and unspecified dementia) were identified from health record linkage. Estimates of residential air pollution, traffic noise, and greenspace exposure have been modelled. Structural brain MRI was conducted from 2014 to 2022, with brain volumes relevant to dementia identified a priori. Associations between environmental exposures, brain volumes, and dementia cases (diagnosed post-MRI) were tested using linear and logistic regression and adjusted for age, sex, household income, ethnicity, education, smoking, and area-level deprivation. Mediation of exposure-outcome associations by plausible brain volumes (those associated with both environmental exposure and dementia outcomes) were modelled using the quasi-Bayesian Monte Carlo method (N = 34,817–39,772).

Results

Small but significant mediating effects (2%-8% of relationships mediated) were observed between PM_2.5abs exposure and dementia risk by reduced total brain volume, NOx and Alzheimer’s disease risk by reduced peripheral cortical grey matter, PM_2.5abs and vascular dementia risk by reduced peripheral cortical grey matter, PM_2.5abs and other dementia risk by reduced total grey matter, and PM₁₀ and other dementia risk by reduced total grey matter. Greenspace and noise were not associated with dementia outcomes in the subset of the cohort providing brain imaging data.

Conclusions

This study adds to existing evidence of associations between environmental exposures and dementia outcomes. Our findings provide novel evidence that differences in brain volume may mediate these relationships. Future research is required to prove this mechanism and establish the other mechanisms through which exposure to air pollution might increase dementia risk.

中文翻译：

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空气污染与英国生物库中 MRI 测量的脑容量介导的痴呆事件之间的纵向关联

 背景

尽管越来越多的证据表明环境暴露与神经退行性疾病的风险有关，但评估人类群体中潜在介质的机制证据仍然有限。

 方法

英国生物样本库是一项大型长期研究，对象为 500,000 年至 2006 年期间招募的 2010 名年龄在 40-69 岁之间的成年人。截至 2022 年的痴呆病例 （阿尔茨海默病、血管性痴呆、其他分类疾病的痴呆和未指明的痴呆） 的 ICD-10 分类报告是从健康记录链接中确定的。对住宅空气污染、交通噪音和绿地暴露的估计值已经建模。2014 年至 2022 年进行了结构性脑部 MRI，先验确定了与痴呆相关的脑体积。使用线性和 logistic 回归测试环境暴露、脑容量和痴呆病例（MRI 后诊断）之间的关联，并针对年龄、性别、家庭收入、种族、教育、吸烟和区域级剥夺进行调整。使用准贝叶斯蒙特卡洛方法（N = 34,817-39,772）建模通过合理的脑体积（与环境暴露和痴呆结果相关的脑体积）对暴露-结果关联的中介。

 结果

通过减少总脑容量观察到 PM_2.5abs 暴露与痴呆风险之间的微小但显着的中介效应（介导的关系的 2%-8%），通过减少外周皮质灰质观察到 NOx 和阿尔茨海默病风险，通过减少外周皮质灰质观察到 PM_2.5abs 和血管性痴呆风险，通过减少总灰质观察到 PM_2.5abs 和其他痴呆风险， 和 PM₁₀ 和其他痴呆风险通过减少总灰质。在提供脑成像数据的队列子集中，绿地和噪音与痴呆结果无关。

 结论

这项研究增加了环境暴露与痴呆结果之间关联的现有证据。我们的研究结果提供了新的证据，表明脑容量的差异可能介导了这些关系。需要未来的研究来证明这种机制，并建立暴露于空气污染可能增加痴呆风险的其他机制。