Exercise and white matter hyperintensities: a randomized clinical trial

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 volume were measured using T2- and proton density-weighted magnetic resonance imaging. Group differences on 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 vs. in-person). Exploratory analysis 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 on 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 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 (vs. 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 resistance exercise training may reduce WMH progression in community-dwelling individuals living with SVCI. This trial is registered with ClinicalTrials.gov, number NCT02669394; submitted for registration on February 1, 2016; first patient enrollment was on May 26, 2016.