Beyond headache: Cognitive improvement in patients with migraine responding to anti-CGRP monoclonal antibodies or botulinum toxin

BackgroundCognitive functioning worsens during migraine attacks and in the interictal period, especially in chronic migraine. This study aims to evaluate whether preventive treatment with anti-CGRP monoclonal antibodies (mAbs) or botulinum toxin (BoNT) improves interictal cognitive performance in migraine patients, and to compare cognitive changes between treatment responders and non-responders, controlling for treatment type.MethodsA two-center prospective longitudinal comparative study of patients with Episodic (EM) or Chronic (CM) migraine receiving either mAbs or BoNT. Participants underwent two comprehensive cognitive evaluations targeting attention/processing speed, executive functions, episodic memory, and language, at baseline (visit 1) and after three to six months of treatment (visit 2). The primary end point was the degree of improvement measured by the z scores of each cognitive domain (adjusted for age and education), from baseline to follow-up, assessed using repeated-measures analysis with time as the within-subject factor and treatment response as the between-subject factor, controlling for treatment group. Treatment response was defined as a decrease in monthly moderate-to-severe headache days of ≥30% in CM or ≥50% in EM at follow-up.ResultsOne hundred patients were included, and 90 completed the study (median age = 42 years, 96.7% women, 58 (64.4%) with CM, 64 (71.1%) treated with mAbs, and 26 (28.8%) with BoNT. Forty-seven (52.2%) were responders (59.4% in the mAbs group and 34.6% in the BoNT group) after a mean follow-up time of 4.5 months. Improvement in a measure of executive functions (comprising tests of working memory, alternating attention, and phonological fluency) was significantly higher in responders than in non-responders, independently of treatment group. No significant differences between responders and non-responders were observed in episodic memory, language, or processing speed. Among responders, the change in executive function score was not associated with the reduction in monthly moderate-severe headache days or the final number of monthly headache-free days.ConclusionsPerformance on measures of executive capacities, may improve in migraine patients after a few months of effective migraine treatment with mAbs or BoNT, regardless of the treatment group. Further research is needed to determine whether this effect augments over time, is associated to the reduction of pre-ictal and post-ictal days and /or to brain networks reorganization.