Exposure to air pollution and risk of incident dementia in the UK Biobank

Abstract

Background: Air pollution may cause inflammatory and oxidative stress damage to the brain, leading to neurodegenerative disease. The association between air pollution and dementia, and modification by apolipoprotein E genotype 4 (APOE-ε4) has yet to be fully investigated.

Objectives: To examine associations of air pollution with three types of incident dementias (Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VAD)), and their potential modification by APOE-ε4 genotype.

Methods: The UK Biobank enrolled >500,000 participants (2006-2010) with ongoing follow-up. We used annual averages of air pollution (PM_2.5, PM₁₀, PM_2.5-10, PM_{2.5absorbance}, NO₂, NO_X) for 2010 scaled to interquartile ranges (IQR). We included individuals aged ≥60 years, with no dementia diagnosis prior to January 1, 2010. Time to incident dementia and follow-up time were reported from baseline (January 01, 2010) to last censor event (death, last hospitalization, or loss to follow-up). Cox proportional hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated to estimate the association of air pollutants and incident dementia, and modification of these associations by APOE-ε4.

Results: Our sample included 187,194 individuals (including N = 680 AD, N = 377 VAD, N = 63 FTD) with a mean follow-up of 7.04 years. We observed consistent associations of PM_2.5 with greater risk of all-cause dementia (HR = 1.17, 95% CI: 1.10, 1.24) and AD (HR = 1.17, 95% CI: 1.06, 1.29). NO₂ was also associated with greater risk of any incident dementia (HR = 1.18, 95% CI: 1.10, 1.25), AD (HR = 1.15, 95% CI: 1.04, 1.28) and VAD (HR = 1.18, 95% CI: 1.03, 1.35). APOE-ε4 did not modify the association between any air pollutants and dementia.

Discussion: PM_2.5 and NO₂ levels were associated with several types of dementia, and these associations were not modified by APOE-ε4. Findings from the UK Biobank support and extend to other epidemiological evidence for the potential association of air pollutants with detrimental brain health during aging.

Keywords: Air pollution; Alzheimer's; Apolipoprotein E4; Dementia; Nitrogen oxides; Particulate matter.

Figure 1:

Study Flow Chart for the complete case analysis of incident all-cause dementia, Alzheimer’s disease, vascular dementia, and frontotemporal dementia.

Figure 2:

Hazard ratios (HR) and 95% confidence intervals (CIs) for incident all-cause dementia associated with IQR (interquartile range) and quartile increments (compared to Q1 referent) in air pollutant levels (μg/m³), with adjustment baseline age, sex, college enrolled, smoking status, income, urban, research center by country and APOE-ε4.

Figure 3:

Hazard ratios (HR) and 95% confidence intervals (CIs) for incident Alzheimer’s Disease (AD) associated with IQR (interquartile range) and quartile increments (compared to Q1 referent) in air pollutant levels (μg/m³), with adjustment for baseline age, sex, college enrolled, smoking status, income, urban, research center and APOE-ε4.

Figure 4:

Hazard ratios (HR) and 95% confidence intervals (CIs) for incident Vascular dementia (VAD) associated with IQR (interquartile range) and quartile increments (compared to Q1 referent) in air pollutant levels (μg/m³), with adjustment baseline age, sex, college enrolled, smoking status, income, urban, research center by country and APOE-ε4.

Figure 5:

Hazard ratios (HR) and 95% confidence intervals (CIs) for incident Frontotemporal dementia (FTD) associated with IQR (interquartile range) and quartile increments (compared to Q1 referent) in air pollutant levels (μg/m³), with adjustment baseline age, sex, college enrolled, smoking status, income, urban, research center by country and APOE-ε4.

Figure 6:

Kaplan-Meier survival curves by (a) PM_2.5 (b) PM_2.5abs (c)PM_2.5–10 (d) PM₁₀ (e) NO₂ (f) NO_X quartiles for Alzheimer’s Disease (AD).