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.