α‑synuclein (α‑Syn) is a highly abundant pre‑synaptic neuronal protein. Misfolding and aggregation of α‑Syn may play a leading role in many mechanisms and processes linked to neurodegenerative diseases related to cognition dysfunction and postoperative neurocognitive disorders. This review focused on the neurotoxic effects of α‑Syn oligomers and research progress on cognition dysfunction. Such mechanisms not only deepen our knowledge regarding the etiology of cognition dysfunction but also open new perspective for therapeutic intervention.