Effects of Physical Activity on Brain White Matter Integrity Are Region-, Dose-, and Age-Dependent: Findings From the Population-Based Rhineland Study.
Overview
- Population Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany
- Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Accare Child Study Center, Groningen, the Netherlands
- The Research School of Behavioural and Cognitive Neurosciences, University of Groningen, Groningen, the Netherlands
- Artificial Intelligence in Medical Imaging, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, University Hospital Bonn, Bonn, Germany
- Centre of Neurology, Clinic for Parkinson, Sleep & Movement Disorders, University of Bonn, University Hospital Bonn, Bonn, Germany
Abstract
White matter integrity is a sensitive marker of cerebrovascular health and aging. Physical activity may promote white matter health, but previous studies were limited by self‐reported activity and small sample sizes. We examined the association between accelerometer‐based physical activity and novel indices of white matter integrity while identifying potential mediators. We analyzed cross‐sectional baseline data from 4188 participants (58% women, mean age: 55.4 years) of the Rhineland Study, a prospective cohort study in Bonn, Germany. Physical activity measures (independent variables) were derived from activPAL3 micro‐accelerometers. Fractional anisotropy, mean diffusivity, free water fraction, orientation dispersion, and neurite density (outcomes) were obtained from 3 T MR images for the whole brain and across 27 white matter tracts. We performed multivariable polynomial regression and mediation analyses for cardiometabolic and inflammatory factors. Higher energy expenditure was related to lower orientation dispersion, with the association leveling off at higher amounts (standardized β linear = −0.153 [−0.183; −0.122]; β quadratic = 0.034 [0.017; 0.051]; both p < 0.001). Physical activity was linked to lower neurite density in motor tracts (βs between −0.133 and −0.056, all p < 0.001). However, with advancing age, physical activity became more strongly associated with higher neurite density and lower mean diffusivity of supratentorial fibers. Body weight, cardiometabolic, and inflammatory factors partly mediated effects of physical activity on white matter microstructure. Physical activity is related to white matter integrity in a nonlinear, age‐ and region‐specific way. Physical activity's effects are greatest in sedentary and older individuals, likely mediated through its impact on body composition, cardiometabolic health, and systemic inflammation.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data Availability Statement
Analytical code will be made available upon request. The data set of the Rhineland Study is not publicly available because of data protection regulations. Access to data can be provided to scientists in accordance with the Rhineland Study's Data Use and Access Policy. Requests for further information or to access the data set of the Rhineland Study should be directed to .
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 6 keywords, 13 MeSH terms, 6 funders, 49 references.
Cite
This paper
Saxler, E., Fox, F. A. U., Koch, A., Yang, X., Zeng, W., Estrada, S., Breteler, M. M. B., & Aziz, N. A. (2026). Effects of Physical Activity on Brain White Matter Integrity Are Region-, Dose-, and Age-Dependent: Findings From the Population-Based Rhineland Study. Aging cell, 25(8), e70659. https://
BibTeX
@article{saxler2026effec
author = {Saxler, Eva and Fox, Fabienne A U and Koch, Alexandra and Yang, Xingwang and Zeng, Weiyi and Estrada, Santiago and Breteler, Monique M B and Aziz, N Ahmad},
title = {{Effects of Physical Activity on Brain White Matter Integrity Are Region-, Dose-, and Age-Dependent: Findings From the Population-Based Rhineland Study}},
journal = {Aging cell},
year = {2026},
month = aug,
volume = {25},
number = {8},
pages = {e70659},
publisher = {Wiley},
issn = {1474-9718},
doi = {10.1111/
url = {https://
pmid = {42568043},
pmcid = {PMC13451344}
}
RIS
TY - JOUR
AU - Saxler, Eva
AU - Fox, Fabienne A U
AU - Koch, Alexandra
AU - Yang, Xingwang
AU - Zeng, Weiyi
AU - Estrada, Santiago
AU - Breteler, Monique M B
AU - Aziz, N Ahmad
TI - Effects of Physical Activity on Brain White Matter Integrity Are Region-, Dose-, and Age-Dependent: Findings From the Population-Based Rhineland Study
T2 - Aging cell
J2 - Aging Cell
PY - 2026
DA - 2026/
VL - 25
IS - 8
SP - e70659
SN - 1474-9718
PB - Wiley
DO - 10.1111/
UR - https://
LA - en
ER -
CSL-JSON
{
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