| Title: | Roles of Genetic Predisposition and Mediation of Biological Age Acceleration in the Association Between Air Pollution and Dementia |
| Journal: | The Journals of Gerontology Series A |
| Published: | 4 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40037565/ |
| DOI: | https://doi.org/10.1093/gerona/glaf046 |
Publication 15655
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Abstract
BACKGROUND: Air pollution exposure (both individual and joint) is associated with dementia, but its relation to early-onset dementia (EOD) and late-onset dementia (LOD) remains inconclusive. Meanwhile, the modification by genetic predisposition and mediation by accelerated biological aging are also unclear.</p>
METHODS: A cohort of 285 774 dementia-free participants from the UK Biobank was analyzed. Exposure levels of four major air pollutants (PM2.5, PM10, NO2, and NOx), two air pollution scores (APS1 and APS2) were obtained, and their associations with all-cause dementia (ACD), EOD and LOD were assessed via Cox models. Genetic predisposition to dementia was evaluated and the mediation role of PhenoAge-Accel was investigated under the counterfactual framework.</p>
RESULTS: During a median follow-up of 13.4 years, 3 898 participants developed ACD, including 231 with EOD and 3 650 with LOD. Per IQR increase of PM2.5, PM10, NO2, NOx, APS1 and APS2 was associated with 6.5% (95%CIs) (2.3%-10.9%), 6.8% (2.2%-11.5%), 4.6% (0%-9.5%), 5.3% (0.7%-10.0%), 6.8% (2.7%-11.1%), or 6.7% (2.2%-11.4%) higher risk of incident ACD, exhibiting a stronger effect on EOD than LOD. Participants with the highest polygenic risk score and air pollution scores possessed the greatest risk of ACD, EOD, and LOD. PhenoAge-Accel moderately mediated the influence of air pollution exposure on ACD risk, especially among low genetic risk participants, with slightly lower mediation effects for EOD than LOD. Similar results were found when adopting KDMAge-Accel.</p>
CONCLUSIONS: Long-term joint exposure to air pollutants exhibited stronger associations with EOD than LOD, and accelerated biological aging serves as a partial mediator in this adverse connection.</p>
14 Keywords
- Aged
- Aging
- Air Pollutants
- Air Pollution
- Dementia
- Environmental Exposure
- Female
- Genetic Predisposition to Disease
- Humans
- Male
- Middle Aged
- Particulate Matter
- Risk Factors
- United Kingdom
11 Authors
- Zhou Jiang
- Yu Yan
- Jike Qi
- Yuxin Liu
- Yuchen Jiang
- Hao Zhang
- Hao Chen
- Xinying Guan
- Pan Zhang
- Ting Wang
- Ping Zeng
1 Application
| Application ID | Title |
|---|---|
| 88159 | Fine-mapping, genetic correlation and genetic risk prediction for complex traits in different populations |
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