Association between interictal high plasma calcitonin gene-related peptide and cognition affection in childhood migraine

Abstract Background Cognitive impairment is recognized as a comorbidity in childhood migraine. Calcitonin Gene-Related Peptide (CGRP) has been involved in migraine pathophysiology, but its relationship with cognitive dysfunction remains unclear. This study investigates the association between interictal CGRP plasma levels and cognitive impairment in pediatric migraineurs. Methods This was a cross-sectional study that was conducted on 89 participants (44 migraine patients and 45 controls) during the period from July 2022 to December 2023. Demographic data, migraine severity, and disability were assessed, and patients were furthermore classified as chronic or episodic migraineurs. During the interictal period (at least two days post-attack), plasma CGRP levels were measured, and neuropsychological functions were evaluated using digit span, similarities, Benton Visual Retention, and Trail Making Tests (TMT). Statistical comparisons were performed between groups. Results We included 44 migraine patients, matched with 45 healthy controls for age, sex, and body mass index (BMI). Migraine patients showed significantly lower scores on the Digit Span ( p = 0.028), Similarities ( p < 0.001), and Benton Visual Retention Tests ( p < 0.001), and required longer completion times on TMTs A and B ( p = 0.001 and p < 0.001, respectively). Additionally, plasma CGRP levels were markedly higher in migraine patients than controls (median 247.05 vs. 27.57 pg/mL, p < 0.001) and in chronic compared with episodic migraine ( p = 0.038). Higher interictal CGRP levels correlated with poorer performance in attention (TMT-A: r = 0.401, p < 0.001), psychomotor speed (TMT-B: r = 0.439, p < 0.001), working memory (Digit Span: r = − 0.294, p = 0.005), and visual memory (Benton-B: r = 0.46, p < 0.001). Conclusion Higher interictal plasma CGRP levels were associated with impaired attention, working memory, visual memory, and psychomotor speed in pediatric migraine, suggesting a potential link between CGRP and cognitive function. Given the cross-sectional design, these findings position CGRP as a candidate biomarker for cognitive dysfunction in pediatric migraine, warranting further validation through longitudinal and mechanistic investigation.