# Cortical Morphology Alterations Mediate the Relationship Between Glymphatic System Function and the Severity of Asthenopia

## TL;DR

This study finds that impaired glymphatic system function is linked to changes in brain structure and increased severity of accommodative asthenopia.

## Contribution

The study introduces DTI-ALPS as a novel method to assess glymphatic function and links it to cortical changes in asthenopia.

## Key findings

- Patients with asthenopia showed increased sulcal depth and cortical thickness in specific brain regions.
- The ALPS index was significantly lower in patients with asthenopia compared to healthy controls.
- Cortical changes partially mediate the relationship between glymphatic dysfunction and asthenopia severity.

## Abstract

Objectives: This study is aimed at assessing glymphatic function by diffusion tensor image analysis along the perivascular space (DTI-ALPS) and its associations with cortical morphological changes and severity of accommodative asthenopia (AA).

Methods: We prospectively enrolled 50 patients with AA and 47 healthy controls (HCs). All participants underwent diffusion tensor imaging (DTI) and T1-weighted imaging and completed the asthenopia survey scale (ASS). Differences in brain morphometry and the analysis along the perivascular space (ALPS) index between the two groups were compared. The correlation and mediation analyses were conducted to explore the relationships between them.

Results: Compared to HCs, patients with AA exhibited significantly increased sulcal depth in the left superior occipital gyrus (SOG.L) and increased cortical thickness in the left superior temporal gyrus (STG.L), left middle occipital gyrus (MOG.L), left postcentral gyrus (PoCG.L), and left precuneus (PCUN.L). Additionally, patients with AA had a significantly lower ALPS index than HCs. The sulcal depth of the SOG.L was significantly positively correlated with the ASS score in patients with AA, and a positive correlation was found between the cortical thickness of the MOG.L and ASS score. The ALPS index was negatively associated with the sulcal depth of the SOG.L and cortical thickness of the MOG.L. Mediation analysis revealed that the sulcal depth of SOG.L and cortical thickness of MOG.L partially mediated the impact of the DTI-ALPS index on the ASS score.

Conclusion: Our findings suggested that patients with AA exhibit impaired glymphatic function, which may contribute to the severity of asthenopia through its influence on cortical morphological changes. The ALPS index is anticipated to become a potential imaging biomarker for patients with AA.

Trial Registration: Chinese Registry of Clinical Trials: ChiCTR1900028306