Physical exercise increases the NODDI-derived neurite density index across white matter tracts in healthy older adults: results from the FIT4BRAIN randomized controlled trial
- 1Jena University Hospital
Abstract
Cross-sectional studies suggest associations between physical exercise and white matter in older adults, but evidence from randomized controlled trials is scarce. Neurite orientation dispersion and density imaging indices are biophysically informed metrics of white matter microstructure. Here, we tested whether a remotely delivered, 8-week multicomponent physical exercise intervention impacts neurite density (NDI) and orientation dispersion (ODI) across major white matter tracts in older adults. This secondary analysis of a randomized controlled trial included participants with available diffusion MRI data (n = 66; age: 66.4 {+/-} 3.6 y; 43 females). Participants were randomized to a multicomponent exercise (PAG, n = 34) or an active control (CON, n = 32) intervention. Intervention effects on NDI/ODI were tested using linear mixed-effects and Bayesian multilevel models adjusted for age and sex. A significant Timepoint x Group interaction was observed for NDI (p = 0.003) but not for ODI (p = 0.785), further confirmed in Bayesian analyses for 22 white matter tracts, indicating a greater increase in NDI in the PAG. The standardized composite VO2max score increased from pre- to post-intervention within the PAG, although the Timepoint x Group interaction was not significant (p = 0.079). Across all participants, pre-to-post changes in mean NDI were positively correlated with changes in VO2max, but this association did not differ between groups. Our results indicate that white matter microstructure remains responsive to short-term, multicomponent physical exercise in older adults.
Significance statementWhite matter microstructure deteriorates with aging. Given the ample health benefits of physical exercise, we investigated whether it can also improve white matter microstructural indices. In this randomized controlled trial, an 8-week remotely delivered multicomponent exercise program increased an MRI-based index of white matter tissue density across major tracts in older adults. These changes were not observed in an active control group. An index of white matter tissue orientation did not show intervention-related changes. Our findings provide experimental evidence that white matter microstructure remains sensitive and responsive to short-term multicomponent physical exercise in later life.
Related
- Effects of mindfulness-based yoga and physical exercise on psychological well-being in individuals with visual impairment: a three-armed randomized controlled trial
- Effects of exercise interventions based on American College of Sports Medicine recommendations on physical function, body composition, and quality of life in older adults with sarcopenia: a meta-analysis of randomized controlled trials
- Effectiveness of a Physical Exercise Prescription Program in Primary Care to Improve Physical Fitness and Quality of Life in Adults Aged 65 Years and Older in a Rural Basic Health Area-Study Protocol for a Randomized Controlled Trial (PREFIS-AP).
- Effects of a Multicomponent Exercise Program on Physical Functions and Quality of Life in Pre-Frail and Frail Women: A Randomized Controlled Trial Protocol
- Impact of supervised physical exercise on inflammatory and oxidative stress biomarkers in older adults: a systematic review and meta-analysis of randomized controlled trials
BibTeX
@misc{ruizrizzo2026physical,
title = {{Physical exercise increases the NODDI-derived neurite density index across white matter tracts in healthy older adults: results from the FIT4BRAIN randomized controlled trial}},
author = {A. L. Ruiz-Rizzo and S. J. Schrenk and S. Brodoehl and C. Frahm and C. Gaser and M. Herbsleb and C. Puta and O. W. Witte and K. Finke},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.26361810},
url = {https://www.medrxiv.org/content/10.64898/2026.08.31.26361810v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Physical exercise increases the NODDI-derived neurite density index across white matter tracts in healthy older adults: results from the FIT4BRAIN randomized controlled trial
AU - A. L. Ruiz-Rizzo
AU - S. J. Schrenk
AU - S. Brodoehl
AU - C. Frahm
AU - C. Gaser
AU - M. Herbsleb
AU - C. Puta
AU - O. W. Witte
AU - K. Finke
PY - 2026
DA - 2026/08/31
PB - medRxiv
DO - 10.64898/2026.08.31.26361810
UR - https://www.medrxiv.org/content/10.64898/2026.08.31.26361810v1
AB - Cross-sectional studies suggest associations between physical exercise and white matter in older adults, but evidence from randomized controlled trials is scarce. Neurite orientation dispersion and density imaging indices are biophysically informed metrics of white matter microstructure. Here, we tested whether a remotely delivered, 8-week multicomponent physical exercise intervention impacts neurite density (NDI) and orientation dispersion (ODI) across major white matter tracts in older adults. This secondary analysis of a randomized controlled trial included participants with available diffusion MRI data (n = 66; age: 66.4 {+/-} 3.6 y; 43 females). Participants were randomized to a multicomponent exercise (PAG, n = 34) or an active control (CON, n = 32) intervention. Intervention effects on NDI/ODI were tested using linear mixed-effects and Bayesian multilevel models adjusted for age and sex. A significant Timepoint x Group interaction was observed for NDI (p = 0.003) but not for ODI (p = 0.785), further confirmed in Bayesian analyses for 22 white matter tracts, indicating a greater increase in NDI in the PAG. The standardized composite VO2max score increased from pre- to post-intervention within the PAG, although the Timepoint x Group interaction was not significant (p = 0.079). Across all participants, pre-to-post changes in mean NDI were positively correlated with changes in VO2max, but this association did not differ between groups. Our results indicate that white matter microstructure remains responsive to short-term, multicomponent physical exercise in older adults. Significance statementWhite matter microstructure deteriorates with aging. Given the ample health benefits of physical exercise, we investigated whether it can also improve white matter microstructural indices. In this randomized controlled trial, an 8-week remotely delivered multicomponent exercise program increased an MRI-based index of white matter tissue density across major tracts in older adults. These changes were not observed in an active control group. An index of white matter tissue orientation did not show intervention-related changes. Our findings provide experimental evidence that white matter microstructure remains sensitive and responsive to short-term multicomponent physical exercise in later life.
ER -