Association between allostatic load and accelerated white matter brain aging: findings from the UK biobank

Li Feng; Zhenyao Ye; Zewen Du; Yezhi Pan; Travis Canida; Hongjie Ke; Song Liu; Shuo Chen; L Elliot Hong; Peter Kochunov; Jie Chen; David K Y Lei; Edmond Shenassa; Tianzhou Ma

doi:10.1093/aje/kwae396

Association between allostatic load and accelerated white matter brain aging: findings from the UK biobank

Am J Epidemiol. 2024 Oct 11:kwae396. doi: 10.1093/aje/kwae396. Online ahead of print.

Authors

Li Feng^{1

2}, Zhenyao Ye^{3

4}, Zewen Du⁵, Yezhi Pan³, Travis Canida⁶, Hongjie Ke², Song Liu⁷, Shuo Chen^{3

4}, L Elliot Hong⁸, Peter Kochunov⁸, Jie Chen⁹, David K Y Lei¹, Edmond Shenassa^{2

10

11

12}, Tianzhou Ma²

Affiliations

¹ Department of Nutrition and Food Science, College of Agriculture & Natural Resources, University of Maryland, College Park, MD, United States.
² Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park, MD, United States.
³ Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, MD, United States.
⁴ Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, MD, United States.
⁵ Department of Biostatistics, School of Global Public Health, New York University, New York, NY, United States.
⁶ Department of Mathematics, The college of Computer, Mathematical, and Natural Sciences, University of Maryland, College Park, MD, United States.
⁷ School of Computer Science and Technology, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China.
⁸ Louis A. Faillace Department of Psychiatry & Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States.
⁹ Department of Health Policy and Management, School of Public Health, University of Maryland, College Park, MD, United States.
¹⁰ Maternal & Child Health Program, School of Public Health, University of Maryland, College Park, MD, United States.
¹¹ Department of Epidemiology, School of Public Health, Brown University, Providence, RI, United States.
¹² Department of Epidemiology & Public Health, School of Medicine, University of Maryland, Baltimore, MD, United States.

PMID: 39393834
DOI: 10.1093/aje/kwae396

Abstract

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29 years in association analysis and by 0.33 years in Mendelian analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64 years old, with no significant sex difference. This study demonstrated that higher chronic stress was significantly associated with accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.

Keywords: Allostatic load; Uk biobank; brain aging; chronic stress; white matter.

© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Abstract

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