Glucagon-Like Peptide-1 Receptor Agonist Therapy and Neurocognitive Outcomes in Medically Managed Idiopathic Intracranial Hypertension: A Propensity Score–Matched Cohort Study

BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) have been shown to reduce invasive interventions and improve symptom control in idiopathic intracranial hypertension (IIH). However, their impact on neurocognitive outcomes remains unknown. METHODS: We used the TriNetX US Collaborative Network to conduct a propensity score-matched study of adults with a first IIH diagnosis from January 2016 to December 2025. The GLP-1RA cohort-initiated therapy within 1 month before to 3 months after diagnosis. Patients with CSF diversion, venous sinus stenting, or pre-existing cognitive or fatigue diagnoses were excluded. Matching balanced demographics, cardiometabolic comorbidities, IIH-directed pharmacotherapy, BMI, and HbA1c. Cognitive decline, dementia composite, fatigue, inpatient admission, and emergency department visits were assessed at 1, 3, and 5 years using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: After matching, 3,652 patients were retained in each cohort. At 5 years, GLP-1RA use was associated with lower event probabilities for cognitive decline, 4.69% versus 7.99%, HR 0.51, 95% CI 0.38-0.69; cognitive decline or dementia, 4.88% versus 8.17%, HR 0.52, 95% CI 0.39-0.69; and fatigue, 11.79% versus 14.88%, HR 0.71, 95% CI 0.59-0.87. Event probabilities were also lower for inpatient admission, 39.24% versus 41.70%, HR 0.70, 95% CI 0.64-0.77; and emergency department visits, 29.55% versus 37.82%, HR 0.69, 95% CI 0.62-0.76. CONCLUSIONS: In medically managed adults with IIH, GLP-1RA therapy was associated with lower risks of incident cognitive decline, cognitive decline or dementia, fatigue, inpatient admission, and emergency department visits. These findings suggest GLP-1RAs improve neurocognitive outcomes and quality of life in IIH.