IRS1 and Cognitive impairment: Conclusions: PD patients with cognitive impairment exhibited lower NEVα-synuclein and pTyr20-IRS-1 and higher pTau181 levels than cognitively intact PD patients.Additionally, α-synuclein and pTyr20- IRS-1 were associated with PD motor symptom severity.Plasma NEVs are a valuable tool for discovering biomarkers in PD.