MR Imaging Indices for Brain Interstitial Fluid Dynamics and the Effects of Orexin Antagonists on Sleep

The purpose of this study was to assess the extent to which improvement in sleep with lemborexant contributed to changes in interstitial fluid dynamics.

The 3 methods including diffusion tensor image analysis along the perivascular space (DTI-ALPS), dynamic contrast-enhanced method to assess tissue vascular permeability (Ktrans), and choroid plexus volume (CPV) were used. Correlations between these imaging indices and sleep parameters (latency to persistent sleep [LPS], wake after sleep onset [WASO], total sleep time [TST], and sleep efficiency [SE]) were evaluated using Pearson correlation analysis. Additionally, multiple regression analysis and linear mixed model analysis were employed to assess the relationship between baseline sleep status and imaging parameter changes. MRI and sleep assessments were performed before treatment initiation (week 0, w0) and at 12 weeks after lemborexant administration (week 12, w12).

The ALPS-index was inversely correlated with LPS and positively correlated with TST and SE at w0. In multiple regression analysis, ALPS-index was lower when sleep parameters other than LPS were poor at w0. A linear mixed model analysis suggested that poor sleep status in LPS and SE at w0 may have an effect on greater ALPS-index. In the evaluation of Ktrans measurement, the single regression analysis showed a statistically significant correlation between the reduction in Ktrans and the shortening in LPS. Examination of CPV and sleep parameters showed a significant negative correlation between TST and CPV at w0 and w12. Multiple regression analysis also showed that TST of w12 had a significant effect on CPV at w12.

Our results suggested that poor sleep status is related to the greater change of ALPS-index and CPV improvement after lemborexant administration may be related to in part to sleep parameter improvement.