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Glucagon-Like Peptide-1 Receptor Agonist Therapy and Neurocognitive Outcomes in Medically Managed Idiopathic
Sabha Ahmed1, Vidhi Dhaduk1, Jay Kakadiya1
1From the Department of Radiology (S.A.), National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India; Department of Neuroradiology (V.D., J. K., A.Y.A., H.J., D.A.L.), Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV; Department of Neurosurgery (H.C.), University of Maryland Medical Center, Baltimore, MD; Department of Radiology (G.B., P.R.), Mayo clinic, Rochester, MN; Department of Radiology (N.S.), Mayo clinic, Jacksonville, FL; Department of Neurosurgery (M.K.M.), Interventional Radiology (M.C.), Oregon Health and Science University, Portland, OR; Department of Neurological Surgery (M.A.E.), Montefiore Medical Center, the University Hospital for Albert Einstein College of Medicine, NY; Department of Neuroradiology (H.A.S.), MD Anderson Cancer Center, Houston, TX; Division of Neuroradiology (V.S.Y.), Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD; Neuroendovascular Program (A.A.D.), Massachusetts General Hospital & Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Neurointerventional & Neuroanalytics Collaboration (NAN-C) (A.A.D.), School of Medicine, Toronto Metropolitan University, Toronto, ON and Department of Radiology (A.M.), Yale New Haven hospital, New Haven CT.
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.
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