Subjective cognitive symptoms improve following effective migraine treatment: A patient-reported outcome study

Our objective was to investigate whether subjective cognitive symptoms improve after effective preventive migraine treatment. Subjective cognitive symptoms, such as memory and concentration difficulties, are increasingly recognized as part of the clinical spectrum of migraine. We aimed to evaluate whether subjective cognitive symptoms improve with effective preventive migraine treatment acting predominantly outside the central nervous system.

We conducted a prospective two-center observational cohort study with a pre-post (within-person) design including adults with migraine diagnosed according to the International Classification of Headache Disorders, 3rd edition criteria, who initiated preventive treatment with either anti-calcitonin gene-related peptide/calcitonin gene-related peptide receptor monoclonal antibodies or onabotulinumtoxinA at two tertiary headache centers in Portugal between October 2023 and August 2025. Treatment response was defined as a ≥50% reduction in monthly moderate to severe headache days in patients with episodic migraine and a ≥30% reduction in those with chronic migraine, assessed between baseline and 3-6 months of follow-up. Subjective cognitive symptoms, assessed using the Subjective Memory Complaints scale, and depression and anxiety symptoms, evaluated with the Hospital Anxiety and Depression Scale, were compared between baseline and follow-up according to treatment responder status.

Participants (N = 96, mean age 42.4±12.0 years, 94/96 [98%] women, 68/96 [71%] with chronic migraine), received either anti-calcitonin gene-related peptide/receptor monoclonal antibodies (n = 65) or onabotulinumtoxinA (n = 31), and 51 responded to treatment. Treatment responders showed greater improvement in subjective cognitive symptoms than nonresponders (B = -2.22, 95% CI = -3.62 to -0.82, p = 0.002), regardless of preventive treatment type (B = 0.17, 95% CI = -1.34 to 1.68, p = 0.825) and baseline depression (B = 0.02, 95% CI = -0.21 to 0.24, p = 0.894) and anxiety (B = -0.06, 95% CI = -0.25 to 0.13, p = 0.545) symptoms. Although in patients with borderline or clinically significant depression symptoms, cognitive improvement was primarily associated with improvement in depression symptoms (B = 0.35, 95% CI = 0.03-0.68, p = 0.033; B = 0.61, 95% CI = 0.32-0.90, p < 0.001; respectively), among patients without baseline depression symptoms, cognitive improvement was only associated with treatment response (B = -1.77, 95% CI = -3.32 to -0.21, p = 0.027).

This study shows that effective preventive treatment is associated with significant improvement in subjective cognitive symptoms, highlighting their responsiveness to treatment and relevance to patient-reported outcomes.