Relaxometry and diffusion MRI reveal sex differences in the association between daytime sleepiness and white matter...

Poor sleep quality is linked to cognitive decline and increased risk for neurological conditions. Additionally, white matter (WM) degeneration is a hallmark of brain aging and neurodegenerative disorders. As myelin is a key component of WM, directly assessing myelin is essential to understanding the relationship between sleep and WM. Previous neuroimaging studies have explored this link using nonspecific magnetic resonance imaging (MRI) proxies for myelin. We examined the relationship between insomnia and daytime sleepiness with WM using quantitative MRI metrics. Myelin was measured using myelin water fraction, a sensitive and specific marker of myelin content. WM integrity was evaluated through individual relaxometry and diffusion MRI metrics, as well as a composite index derived from principal component analysis of all quantitative MRI measures. The Women's Health Initiative Insomnia Rating Scale was used to assess insomnia and the Epworth Sleepiness Scale (ESS) for daytime sleepiness. Linear regressions assessed associations between sleep and both individual and composite WM metrics, adjusting for relevant covariates. Results showed that poorer ESS scores were significantly associated with lower WM integrity and lower myelination, particularly across relaxometry-based metrics. We found a significant ESS × sex interaction, with a stronger association between poor sleep and lower WM integrity among females compared to males. These sex differences were even more pronounced in the composite index. This varying association between sleepiness and WM by sex provides a potential avenue for understanding differential vulnerability to neurodegeneration and highlights the need for future sex-specific investigations into the role of sleep in demyelination and brain aging.