| Popis: |
ObjectiveNF1-associated cognitive impairments carry significant life-long morbidity. The lack of targeted biologic treatments remains a significant unmet need. We examine changes in cognition in patients with NF1 in the first 48 weeks of MEK inhibitor (MEKi) treatment.Methods59 NF1 patients ages 5-27 on a MEKi clinical trial treating plexiform neurofibroma underwent pre-treatment and follow-up cognitive assessments over 48-weeks of treatment. Performance tasks (Cogstate) and observer-reported functioning (BRIEF) were primary outcomes. Group-level (pairedt-tests) and individual-level analyses (reliable change index; RCI) were used.ResultsAnalysis showed statistically significant improvements on BRIEF compared to baseline (24-week BRI:t(58)=3.03,p=.004,d=0.24; 48-week MCI:t(39)=2.70,p=.01,d=0.27). RCI indicated more patients had clinically significant improvement at 48-weeks than expected by chance (Chi Square=11.95,p=.001, OR=6.3). Group-level analyses indicated stable performance on Cogstate (p>.05). RCI statistics showed high proportions of improved working memory (24-weeksChi Square=8.36,p=.004, OR=4.6 and 48-weeksChi Square=9.34,p=.004, OR=5.3) but not visual learning/memory. Patients with baseline impairments on BRIEF were more likely to show significant improvement than non-impaired patients (24-weeks 46% v. 8%;Chi Square=9.54,p=.008, OR=9.22; 48-weeks 63% v. 16%;Chi Square=7.50,p=.02, OR=9.0).InterpretationOur data shows no evidence of neurotoxicity in 48-weeks of treatment with a MEKi and a potential clinical signal supporting future research of MEKi as a cognitive intervention. |
