{ "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.", "abstract_shown": true, "affiliations": [ "Department of Health, Kinesiology, and Applied Physiology, Faculty of Arts and Science, Concordia University, Montréal, Canada H4B 1R6.", "Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 1Z3.", "Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 2B5.", "Centre for Aging SMART at Vancouver Coastal Health, Vancouver Coastal Health Research Institute, Vancouver, Canada V5Z 1M9.", "School of Biomedical Engineering, University of British Columbia, Vancouver, Canada V6T 1Z3.", "Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 1Z3.", "Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia 12372.", "Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver Canada V6T 1Z3.", "International Collaboration on Repair Discoveries, Blusson Spinal Cord Centre, Vancouver General Hospital, Vancouver Canada V5Z 1M9.", "Hotchkiss Brain Institute, University of Calgary, Calgary, Canada T2N 4N1.", "Faculty of Kinesiology, University of Calgary, Calgary, Canada T2N 1N4.", "Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.", "Division of Neurology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada V6T 1Z3.", "Vancouver Stroke Program, University of British Columbia, Vancouver, Canada V6T 1Z3." ], "article_type": "research article", "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0, 1, 2, 3 ], "name": "Nárlon C Boa Sorte Silva", "orcid": "0000-0002-4847-3742" }, { "affs": [ 2, 3, 4, 5 ], "name": "Roger C Tam" }, { "affs": [ 6, 7 ], "name": "Walid A Alkeridy", "orcid": "0000-0002-1161-8354" }, { "affs": [ 7 ], "name": "Kevin Lam" }, { "affs": [ 2, 5, 8 ], "name": "Elizabeth Dao" }, { "affs": [ 2, 9, 10 ], "name": "Cindy K Barha" }, { "affs": [ 1, 2, 3 ], "name": "Ryan S Falck" }, { "affs": [ 11 ], "name": "Chun Liang Hsu" }, { "affs": [ 2, 12 ], "name": "Ging-Yuek Robin Hsiung" }, { "affs": [ 3, 7 ], "name": "Ken M Madden" }, { "affs": [ 2, 12, 13 ], "name": "Thalia S Field" }, { "affs": [ 1, 2, 3 ], "name": "Teresa Liu-Ambrose", "orcid": "0000-0002-8297-5308" } ], "bibtex": "https://research.draconitic.com/paper/80g7zb3s110bj.bib", "cited_by": 0, "doi": "10.1093/braincomms/fcag381", "fulltext_url": "https://europepmc.org/articles/PMC13711657", "id": "80g7zb3s110bj", "issns": [ "2632-1297" ], "landing_url": "https://europepmc.org/article/MED/42948654", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "AcademicSubjects/MED00310" ], [ "heading", "AcademicSubjects/SCI01870" ], [ "heading", "Clinical Trial" ], [ "openalex", "2728|Cerebrovascular and genetic disorders" ] ], "openalex": "W7221059006", "pdf_url": "https://europepmc.org/articles/PMC13711657?pdf=render", "pmcid": "PMC13711657", "pmid": "42948654", "published": "2026-10-08", "publisher": "Oxford University Press", "ris": "https://research.draconitic.com/paper/80g7zb3s110bj.ris", "sources": [ { "first_seen": "2026-10-31T00:20:34Z", "native_id": "MED:42948654", "source": "europepmc", "url": "https://europepmc.org/article/MED/42948654" }, { "first_seen": "2026-10-31T12:22:24Z", "native_id": "PMC13711657", "source": "pmc", "url": "https://doi.org/10.1093/braincomms/fcag381" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2728|Cerebrovascular and genetic disorders", "subfield": "neurology" } ], "title": "Exercise and white matter hyperintensities: a randomized clinical trial.", "title_text": "Exercise and white matter hyperintensities: a randomized clinical trial.", "type": "peer-reviewed", "updated_at": "2026-10-31T12:22:24Z", "url": "https://research.draconitic.com/paper/80g7zb3s110bj", "venue": "Brain communications", "versions": [] }