Accelerated biological aging and brain structural alterations linking air pollution to dementia risk: a prospective cohort study - 03/04/26

Doi : 10.1016/j.jnha.2026.100836

Ruoyao Huang ^a,^b, Yacong Bo ^c,^d, Jing Guo ^e, Yang Liu ^c, Chunlei Li ^c, Jintao Han ^c, Shuo Lu ^c, Xiangying Suo ^c,⁎

^a Office of Hospital Administration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

^b National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

^c School of Public Health, Zhengzhou University, Zhengzhou 450001, China

^d NHC Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou 450002, China

^e School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou 450001, China

^⁎ Corresponding author.

Abstract

Objectives

To examine the association of air pollution with dementia and brain structural alternations, and further to explore the mediating role of accelerated biological aging and brain atrophy in the air pollution-dementia association.

Design

A prospective cohort study.

Setting and participants

A total of 488,348 UK Biobank participants without dementia were included at baseline.

Exposure

Air pollution, including PM _2.5 , PM ₁₀ , PM _2.5 absorbance, NO _2, and NO _x .

Measurements

Cox proportional hazards regression models were used to evaluate the association between air pollution and incident dementia, while linear regression models were used to assess its associations with global and 80 regional brain structures. The mediating roles of biological aging acceleration (measured by Klemera-Doubal method Biological Age [KDM-BA] and PhenoAge) and brain structures in the air pollution-dementia association were evaluated using structural equation modeling (SEM).

Results

Compared to participants with the lowest tertile of air pollution exposure, those in the highest exposure group had higher risks of dementia (HR [95%CI]: 1.14 [1.08, 1.21] for PM _2.5 ; 1.09 [1.03, 1.16] for PM ₁₀ ; 1.09 [1.03, 1.16] for PM _2.5 absorbance; 1.20 [1.13, 1.28] for NO ₂ ; and 1.14 [1.08, 1.21] for NO _X ). Air pollution exposure was inversely associated with global and several regional brain structural alterations. SEM revealed a consistent mediating pathway that integrates biological aging and brain structural alterations in the association between air pollution exposure and the risk of dementia.

Conclusions

Our findings support the association between air pollution and dementia, as well as a reduction in global and several regional brain volumes. Notably, biological age acceleration and brain atrophy mediated the air pollution-dementia association.

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Keywords : Dementia, Air pollution, Biological aging, Brain structure

Abbreviations : DALYs, PM, NO _X , NO ₂ , ESCAPA, GIS, GMV, WMV, IDPs, SD, KDM-BA, AA, IQR, CI, EPINEF, HR, RCS, CVD, SEM, FDR