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Age-related cognitive decline can eventually lead to dementia, the most common mental illness in elderly people and an immense challenge for patients, their families and caregivers. Cholinesterase inhibitors constitute the most commonly used antidementia prescription medication. The standardized Ginkgo biloba leaf extract EGb 761® is approved for treating age-associated cognitive impairment and has been shown to improve the quality of life in patients suffering from mild dementia. In an animal model of cognitive aging, we compared the effect of combined treatment with EGb 761® or donepezil monotherapy and vehicle. We compared the effect of chronic treatment (15 days pretreatment) with donepezil (1,5 mg/kg p. o.), EGb 761® (100 mg/kg p. o.), or the combination of the two drugs, or vehicle in 18 – 20 months old male OFA (SD) rats. Learning and memory performance were assessed by Morris water maze testing, motor behavior in an Open field paradigm. In addition to chronic treatment, the substances were administered orally 30 minutes before testing. Compared to the first day and to the control group, only the combination group showed a significant reduction in latency to reach the hidden platform on the second day of testing. There were no effects on motor behavior. These results suggest a superiority of the combined treatment of donepezil with EGb 761® compared to monotherapy.