The potential role of sleep quality in the relationship between glymphatic function and migraine frequency: Insights from a cross-sectional study.

OBJECTIVE

This study aimed to explore the association between glymphatic function, as assessed by the diffusion tensor imaging along perivascular space (DTI-ALPS) index, and headache frequency in individuals with migraine. Additionally, it evaluated whether sleep quality modulates this relationship.

BACKGROUND

Migraine has a complex pathophysiology involving genetic predispositions, comorbidities, and psychosocial factors. Emerging evidence highlights the glymphatic system-responsible for brain waste clearance-as a potential contributor to migraine pathogenesis. As poor sleep quality exacerbates glymphatic dysfunction, it might have an impact on migraine chronification.

METHODS

This cross-sectional study included 106 individuals with migraine (80.2% female; median age: 45.0 years, interquartile range = 37.0-52.0) between June 2018 and February 2020. Glymphatic function was assessed using the DTI-ALPS index derived from brain magnetic resonance imaging, whereas sleep quality was evaluated with the Pittsburgh Sleep Quality Index. First, we evaluated the association between DTI-ALPS index and monthly headache days. A second model included the dichotomized Pittsburgh Sleep Quality Index score ("poor" vs. "good" sleepers) and its interaction with the DTI-ALPS index to examine the moderating role of sleep quality in the relationship between glymphatic function and monthly headache days.

RESULTS

Higher DTI-ALPS index values were associated with fewer monthly headache days in the overall sample while controlling for age and sex (adjusted Incidence Rate Ratio [IRR] = 0.37; 95% confidence interval [CI] = 0.16-0.86, p = 0.020). Additionally, there was a significant interaction between DTI-ALPS index and sleep quality (adjusted IRR = 0.13; 95% CI = 0.02-0.76, p = 0.024) in predicting monthly headache days. We found an association between lower DTI-ALPS and higher headache days only in participants with poor sleep quality (adjusted IRR = 0.21; 95% CI = 0.08-0.59, p = 0.003) whereas no association was found in good sleepers (adjusted IRR = 1.66; 95% CI = 0.38-7.16, p = 0.500). Results remained consistent after adjusting for clinical variables such as disease duration, medication overuse, cutaneous allodynia, aura status, and migraine subtype.

CONCLUSION

Poor sleep quality moderates the association between glymphatic dysfunction and monthly headache days. The results highlight the potential importance of sleep interventions in managing migraine and improving brain glymphatic function.