Association of Long-term Exposure to Ambient Air Pollution With Cognitive Decline and Alzheimer's Disease-Related Amyloidosis

Ya-Hui Ma; Hua-Shuai Chen; Cong Liu; Qiu-Shi Feng; Lei Feng; Ya-Ru Zhang; Hao Hu; Qiang Dong; Lan Tan; Hai-Dong Kan; Can Zhang; John Suckling; Yi Zeng; Ren-Jie Chen; Jin-Tai Yu

doi:10.1016/j.biopsych.2022.05.017

Association of Long-term Exposure to Ambient Air Pollution With Cognitive Decline and Alzheimer's Disease-Related Amyloidosis

Biol Psychiatry. 2023 May 1;93(9):780-789. doi: 10.1016/j.biopsych.2022.05.017. Epub 2022 May 18.

Authors

Ya-Hui Ma¹, Hua-Shuai Chen², Cong Liu³, Qiu-Shi Feng⁴, Lei Feng⁵, Ya-Ru Zhang⁶, Hao Hu⁷, Qiang Dong⁶, Lan Tan⁷, Hai-Dong Kan³, Can Zhang⁸, John Suckling⁹, Yi Zeng¹⁰, Ren-Jie Chen¹¹, Jin-Tai Yu¹²

Affiliations

¹ Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China; Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
² School of Business, Xiangtan University, Xiangtan, Hunan, China.
³ School of Public Health, Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, China.
⁴ Department of Sociology, National University of Singapore, Singapore.
⁵ Department of Psychological Medicine and Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Healthy Longevity, National University Health System, Singapore.
⁶ Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
⁷ Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
⁸ Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
⁹ Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
¹⁰ Center for the Study of Aging and Human Development, Medical School of Duke University, Center for Healthy Aging and Development Studies, National School of Development, Raissun Institute for Advanced Studies, Peking University, Beijing, China.
¹¹ School of Public Health, Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, China. Electronic address: chenrenjie@fudan.edu.cn.
¹² Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: jintai_yu@fudan.edu.cn.

PMID: 35953319
DOI: 10.1016/j.biopsych.2022.05.017

Abstract

Background: Air pollution induces neurotoxic reactions and may exert adverse effects on cognitive health. We aimed to investigate whether air pollutants accelerate cognitive decline and affect neurobiological signatures of Alzheimer's disease (AD).

Methods: We used a population-based cohort from the Chinese Longitudinal Healthy Longevity Survey with 31,573 participants and a 10-year follow-up (5878 cognitively unimpaired individuals in Chinese Longitudinal Healthy Longevity Survey followed for 5.95 ± 2.87 years), and biomarker-based data from the Chinese Alzheimer's Biomarker and Lifestyle study including 1131 participants who underwent cerebrospinal fluid measurements of AD-related amyloid-β (Aβ) and tau proteins. Cognitive impairment was determined by education-corrected performance on the China-Modified Mini-Mental State Examination. Annual exposures to fine particulate matter (PM_2.5), ground-level ozone (O₃), and nitrogen dioxide (NO₂) were estimated at areas of residence. Exposures were aggregated as 2-year averages preceding enrollments using Cox proportional hazards or linear models.

Results: Long-term exposure to PM_2.5 (per 20 μg/m³) increased the risk of cognitive impairment (hazard ratio, 1.100; 95% CI: 1.026-1.180), and similar associations were observed from separate cross-sectional analyses. Exposures to O₃ and NO₂ yielded elevated risk but with nonsignificant estimates. Individuals exposed to high PM_2.5 manifested increased amyloid burdens as reflected by cerebrospinal fluid-AD biomarkers. Moreover, PM_2.5 exposure-associated decline in global cognition was partly explained by amyloid pathology as measured by cerebrospinal fluid-Aβ₄₂/Aβ₄₀, P-tau/Aβ₄₂, and T-tau/Aβ₄₂, with mediation proportions ranging from 16.95% to 21.64%.

Conclusions: Long-term exposure to PM_2.5 contributed to the development of cognitive decline, which may be partly explained by brain amyloid accumulation indicative of increased AD risk.

Keywords: Air pollution; Alzheimer’s disease; Brain amyloidosis; Cerebrospinal fluid; Cognitive decline; Mediation effect.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Air Pollution* / adverse effects
Alzheimer Disease* / pathology
Amyloid beta-Peptides
Amyloidosis* / chemically induced
Biomarkers / cerebrospinal fluid
Cognitive Dysfunction* / etiology
Cross-Sectional Studies
Humans
Nitrogen Dioxide / analysis
Particulate Matter / adverse effects

Substances

Nitrogen Dioxide
Amyloid beta-Peptides
Particulate Matter
Biomarkers