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Trials with interferon-alpha (IFN-α) have provided contradictory findings regarding the presence of cognitive side effects. The development of depression in some patients also raises questions about whether cognitive dysfunction might be secondary to an organic, interferon-induced mood disorder. Thirty patients with chronic myelogenous leukemia were examined before and during treatment with IFN-α alone or IFN-α and chemotherapy. Increased depressive symptoms and declines in information processing and executive functions were observed, but depression alone could not account for cognitive dysfunction. There was some evidence suggesting that exposure to chemotherapy and higher cumulative IFN-α dose may contribute to cognitive impairment.