DOI: 10.1002/alz.080740 ISSN: 1552-5260

Can exercise benefit cerebral white matter myelin? Findings from a 12‐month randomized controlled trial in older adults with vascular cognitive impairment

Nárlon Cássio Boa Sorte Silva, Elizabeth Dao, Chun Liang Hsu, Roger Tam, Kevin Lam, Walid Ahmed Alkeridy, Cornelia Laule, Irene M Vavasour, Ryan G Stein, Teresa Liu‐Ambrose
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Cerebral small vessel disease is a major underlying cause of subcortical ischemic vascular cognitive impairment (SIVCI). Myelin loss is a feature of cerebral small vessel disease, which may underly cognitive and functional decline in older adults living with SIVCI. Resistance training (RT) is a form of exercise associated with slower progression of white matter lesions, a cerebral small vessel disease marker. However, it remains to be determined whether RT can counteract myelin loss in individuals living with SIVCI. Thus, we examined the impact of a 12‐month, twice‐weekly progressive RT program on myelin content in those with SIVCI.


This was a sub‐study of a 12‐month single‐blinded, randomized controlled trial. Participants (n = 91) were randomized to RT or an active control group (balance and tone exercises [BAT]). Study eligibility included: 1) age 55 years and older; 2) magnetic resonance imaging (MRI) evidence of cerebral small vessel disease; 3) mild cognitive impairment; and 4) the absence of dementia. Myelin was measured using a multi‐echo gradient and spin echo T2 relaxation MRI sequence, indexed as myelin water fraction (MWF). Differences between groups at 12 months were assessed via analysis of covariance adjusting for baseline MWF and estimated intracranial volume. MWF data from fifteen white matter tracts were analyzed. Post‐hoc regressions were conducted to determine if changes in MWF were associated with changes in mobility measured with the Short Physical Performance Battery (SPPB).


Seventy‐three participants (RT = 36) aged 74.1 (SD = 5.7), 64% females with high‐quality MRI data were included in the analyses. At 12 months, RT showed lower MWF levels compared with BAT in the genu of the corpus callosum (estimated mean difference [RT – BAT]: ‐0.610, 95% CI: ‐1.041 to ‐0.178, p = 0.006), fornix (‐0.883, 95% CI: ‐1.570 to ‐0.197, p = 0.012), and combined white matter tracts (‐0.326, 95% CI: ‐0.643 to ‐0.009, p = 0.044). Changes in MWF in the combined white matter tracs were positively associated with changes in SPPB (Unstandardized B = 0.124, SE = 0.061, p = 0.047).


Contrary to our expectations, 12 months of balance and tone exercises, but not RT, showed positive changes in myelin. These improvements may result in better mobility in older adults with SIVCI.

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