Effects of MAO ‐B Inhibitors on Cognition in Patients with Parkinson's Disease: A Systematic Network Meta‐Analysis

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder accompanied by cognitive impairment, which increases a risk of dementia as the condition progresses. Although monoamine oxidase B (MAO-B) inhibitors, such as selegiline, rasagiline and safinamide, are used to treat motor symptoms in PD, their impacts on cognitive performance remain unclear. OBJECTIVES: This study systematically evaluated and compared the impacts of MAO-B inhibitors on global cognitive performance and performance of individual cognitive domains in patients with PD. METHODS: Databases were searched through PubMed/Medline, Embase, and Cochrane Library from the inception to May 30, 2025. Thirteen randomized controlled trials (RCTs) evaluating cognitive outcomes in patients with PD treated with selegiline, rasagiline or safinamide were included. Standardized mean differences (SMDs) for global cognition and five cognitive sub-domains were pooled, respectively, using random-effects models. Publication bias and methodological quality were also assessed. RESULTS: 13 RCTs met inclusion criteria. Network meta-analysis showed that only rasagiline significantly improved global cognition compared to placebo (SMD, 0.863; 95% CI, 0.064-1.663), whereas selegiline and safinamide did not show any statistical difference when compared to placebo. None of the MAO-B inhibitors demonstrated significant effects on specific cognitive sub-domains (ie, attention, executive function, memory, language, and visuospatial abilities). CONCLUSIONS: Rasagiline may provide global cognitive benefits in PD, but MAO-B inhibitors, including rasagiline, generally did not demonstrate significant effects on individual cognitive domains. These findings suggest limited cognitive impacts of MAO-B inhibitors beyond managing the motor symptoms. Further large-scale, long-term studies using domain-specific cognitive assessments are warranted to clarify their roles in cognitive performance in patients with PD.