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

  • Ya-Hui Ma
    Affiliations
    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
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  • Hua-Shuai Chen
    Affiliations
    School of Business, Xiangtan University, Xiangtan, Hunan, China
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  • Cong Liu
    Affiliations
    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
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  • Qiu-Shi Feng
    Affiliations
    Department of Sociology, National University of Singapore, Singapore
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  • Lei Feng
    Affiliations
    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
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  • Ya-Ru Zhang
    Affiliations
    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
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  • Hao Hu
    Affiliations
    Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
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  • Qiang Dong
    Affiliations
    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
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  • Lan Tan
    Affiliations
    Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
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  • Hai-Dong Kan
    Affiliations
    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
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  • Can Zhang
    Affiliations
    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
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  • John Suckling
    Affiliations
    Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
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  • Yi Zeng
    Affiliations
    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
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  • Ren-Jie Chen
    Correspondence
    Ren-Jie Chen, Ph.D.
    Affiliations
    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
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  • Jin-Tai Yu
    Correspondence
    Address correspondence to Jin-Tai Yu, M.D., Ph.D.
    Affiliations
    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
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      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 (PM2.5), 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 PM2.5 (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 PM2.5 manifested increased amyloid burdens as reflected by cerebrospinal fluid–AD biomarkers. Moreover, PM2.5 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 PM2.5 contributed to the development of cognitive decline, which may be partly explained by brain amyloid accumulation indicative of increased AD risk.

      Keywords

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