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Peer-reviewedCC BYBrain communications

Exercise and white matter hyperintensities: a randomized clinical trial.

  • Nárlon C Boa Sorte Silva1,2,3,4
  • Roger C Tam3,4,5,6
  • Walid A Alkeridy7,8
  • Kevin Lam8
  • Elizabeth Dao3,6,9
  • Cindy K Barha3,10,11
  • Ryan S Falck2,3,4
  • Chun Liang Hsu12
  • Ging-Yuek Robin Hsiung3,13
  • Ken M Madden4,8
  • Thalia S Field3,13,14
  • Teresa Liu-Ambrose2,3,4
14 affiliations
  1. 1Department of Health, Kinesiology, and Applied Physiology, Faculty of Arts and Science, Concordia University, Montréal, Canada H4B 1R6.
  2. 2Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 1Z3.
  3. 3Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 2B5.
  4. 4Centre for Aging SMART at Vancouver Coastal Health, Vancouver Coastal Health Research Institute, Vancouver, Canada V5Z 1M9.
  5. 5School of Biomedical Engineering, University of British Columbia, Vancouver, Canada V6T 1Z3.
  6. 6Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 1Z3.
  7. 7Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia 12372.
  8. 8Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver Canada V6T 1Z3.
  9. 9International Collaboration on Repair Discoveries, Blusson Spinal Cord Centre, Vancouver General Hospital, Vancouver Canada V5Z 1M9.
  10. 10Hotchkiss Brain Institute, University of Calgary, Calgary, Canada T2N 4N1.
  11. 11Faculty of Kinesiology, University of Calgary, Calgary, Canada T2N 1N4.
  12. 12Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
  13. 13Division of Neurology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 1Z3.
  14. 14Vancouver Stroke Program, University of British Columbia, Vancouver, Canada V6T 1Z3.
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Abstract

Subcortical vascular cognitive impairment (SVCI) is a risk factor for dementia. White matter hyperintensity (WMH) lesions are considered a hallmark of SVCI. We investigated the impact of progressive resistance exercise training (RT) on WMH in individuals with SVCI. This 12-month, single-blinded, proof-of-concept randomized clinical trial involved 89 community-dwelling individuals aged 55 years or older living with SVCI. Participants were randomized (1:1 ratio) to twice-weekly (60 min/day) RT (n = 44) or a balance and tone (BAT, n = 45) control intervention. Whole-brain and region-specific WMH volumes were measured using T₂- and proton density-weighted magnetic resonance imaging. Group differences in the 12-month change in WMH from baseline were determined via analysis of covariance, adjusting for baseline WMH, intracranial volume, age, sex and training format (remote versus in-person). Exploratory analyses tested associations between changes in WMH and changes in growth factors. Participants were mostly females (n = 58, 65.17%) with an average of 74.50 (SD 5.71) years. There were no differences between groups in whole-brain WMH volume after 12 months [estimated mean difference (95% CI): -0.016 (-0.052 to 0.019) log-transformed cm³, P = 0.364]. Region-specific analysis showed main effects of training on WMH volume in the temporal lobe [-0.115 (-0.207 to -0.023), P = 0.015] and splenium of the corpus callosum [-0.120 (-0.215 to -0.025), P = 0.014], favouring the RT group. There was a significant group-by-sex interaction, indicating that intervention effects varied by sex [estimated mean difference-of-differences (95% CI) = -0.093 (-0.170 to -0.016), P = 0.019]. Post hoc contrasts showed that RT (versus BAT) significantly reduced whole-brain WMH volume in female [-0.049 (-0.093 to -0.005), P = 0.029] but not male [0.044 (-0.017 to 0.105), P = 0.152] participants. Exploratory analysis showed that increasing levels of vascular endothelial growth factor [standardized β (95% CI) = -0.503 (-0.838 to -0.167), P = 0.004] were associated with a reduction in whole-brain WMH volume. No associations between insulin-like growth factor 1 and WMH volumes were found (all P > 0.05). Based on these findings, we conclude that progressive RT may reduce WMH progression in community-dwelling individuals living with SVCI. This trial is registered with ClinicalTrials.gov, number NCT02669394; submitted for registration on 1 February 2016; the first patient enrolment was on 26 May 2016.

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Cite

BibTeXRIS
BibTeX
@article{silva2026exercise,
  title = {{Exercise and white matter hyperintensities: a randomized clinical trial.}},
  author = {Nárlon C Boa Sorte Silva and Roger C Tam and Walid A Alkeridy and Kevin Lam and Elizabeth Dao and Cindy K Barha and Ryan S Falck and Chun Liang Hsu and Ging-Yuek Robin Hsiung and Ken M Madden and Thalia S Field and Teresa Liu-Ambrose},
  journal = {Brain communications},
  year = {2026},
  month = oct,
  doi = {10.1093/braincomms/fcag381},
  url = {https://europepmc.org/article/MED/42948654},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Exercise and white matter hyperintensities: a randomized clinical trial.
AU  - Nárlon C Boa Sorte Silva
AU  - Roger C Tam
AU  - Walid A Alkeridy
AU  - Kevin Lam
AU  - Elizabeth Dao
AU  - Cindy K Barha
AU  - Ryan S Falck
AU  - Chun Liang Hsu
AU  - Ging-Yuek Robin Hsiung
AU  - Ken M Madden
AU  - Thalia S Field
AU  - Teresa Liu-Ambrose
PY  - 2026
DA  - 2026/10/08
JO  - Brain communications
DO  - 10.1093/braincomms/fcag381
UR  - https://europepmc.org/article/MED/42948654
AB  - Subcortical vascular cognitive impairment (SVCI) is a risk factor for dementia. White matter hyperintensity (WMH) lesions are considered a hallmark of SVCI. We investigated the impact of progressive resistance exercise training (RT) on WMH in individuals with SVCI. This 12-month, single-blinded, proof-of-concept randomized clinical trial involved 89 community-dwelling individuals aged 55 years or older living with SVCI. Participants were randomized (1:1 ratio) to twice-weekly (60 min/day) RT (n = 44) or a balance and tone (BAT, n = 45) control intervention. Whole-brain and region-specific WMH volumes were measured using T₂- and proton density-weighted magnetic resonance imaging. Group differences in the 12-month change in WMH from baseline were determined via analysis of covariance, adjusting for baseline WMH, intracranial volume, age, sex and training format (remote versus in-person). Exploratory analyses tested associations between changes in WMH and changes in growth factors. Participants were mostly females (n = 58, 65.17%) with an average of 74.50 (SD 5.71) years. There were no differences between groups in whole-brain WMH volume after 12 months [estimated mean difference (95% CI): -0.016 (-0.052 to 0.019) log-transformed cm³, P = 0.364]. Region-specific analysis showed main effects of training on WMH volume in the temporal lobe [-0.115 (-0.207 to -0.023), P = 0.015] and splenium of the corpus callosum [-0.120 (-0.215 to -0.025), P = 0.014], favouring the RT group. There was a significant group-by-sex interaction, indicating that intervention effects varied by sex [estimated mean difference-of-differences (95% CI) = -0.093 (-0.170 to -0.016), P = 0.019]. Post hoc contrasts showed that RT (versus BAT) significantly reduced whole-brain WMH volume in female [-0.049 (-0.093 to -0.005), P = 0.029] but not male [0.044 (-0.017 to 0.105), P = 0.152] participants. Exploratory analysis showed that increasing levels of vascular endothelial growth factor [standardized β (95% CI) = -0.503 (-0.838 to -0.167), P = 0.004] were associated with a reduction in whole-brain WMH volume. No associations between insulin-like growth factor 1 and WMH volumes were found (all P > 0.05). Based on these findings, we conclude that progressive RT may reduce WMH progression in community-dwelling individuals living with SVCI. This trial is registered with ClinicalTrials.gov, number NCT02669394; submitted for registration on 1 February 2016; the first patient enrolment was on 26 May 2016.
SN  - 2632-1297
ER  -