Myelin Changes in Poor Sleepers: Insights into Glymphatic Clearance Function and Regional Circadian Clock Gene Expression

Sleep is essential for maintaining brain myelin integrity. Emerging evidence suggests that poor sleep quality compromises the glymphatic system, a perivascular network crucial for brain waste clearance, leading to the accumulation of neuroinflammatory and toxic proteins, which may affect myelin integrity. Furthermore, poor sleep quality results in alterations in gene expression within the brain. We evaluated the associations among poor sleep quality, brain myelin integrity, and glymphatic clearance function as well as the impact of circadian clock gene expression on regional cortical myelin content. 50 poor sleepers (average age 71.08 ± 4.69 years; Pittsburgh Sleep Quality Index [PSQI] &;gt 5) and 50 good sleepers (average age 73.04 ± 5.80 years; PSQI ≤ 5) were assessed. Myelin volume fraction (MVF) was quantified using magnetization transfer saturation imaging, and glymphatic function was noninvasively examined using diffusion tensor imaging along the perivascular space. Circadian gene expression was analyzed using postmortem brain tissue from the Allen Human Brain Atlas. Magnetic resonance imaging measures were correlated with cognitive and depression scores. Lower MVF was observed in the fronto-temporo-parietal and limbic regions as well as in major white matter tracts in poor sleepers compared with that in good sleepers. This reduction was linked to lower cognitive function scores and higher depressive scores. Poor sleepers also exhibited lower diffusivity along the perivascular spaces, mediating the relationship between poor sleep quality and demyelination. Regions with higher expression of CLOCK, CRY2, PER1, and PER2 exhibited greater MVF disparities between good and poor sleepers, whereas lower expression of CRY1 was associated with more pronounced differences. Poor sleep quality was associated with lower brain myelin integrity, correlating with reduced cognitive performance and increased depressive symptoms. These changes might be mediated by glymphatic clearance dysfunction and were associated with the differential expression of circadian clock genes.