Grant: Operating Grant

Cancer patients who undergo chemotherapy, especially women with breast cancer, often complain of cognitive disturbances ('chemobrain'). The complaints, which include memory loss, attentional difficulties, and poor problem solving abilities, are usually accompanied by a decline in quality of life. Despite a decade of clinical research that pointed to chemotherapy-induced cognitive impairment (CICI), the medical community was slow to accept this relationship. The persistent disagreement prompted calls for animal models to investigate the effects of chemotherapy on cognition under rigorously controlled conditions. In the first systematic attempt to develop a suitable animal model, our group assessed the performance of adult female mice, treated with anti-cancer drugs, on cognitive tests that measure various aspects of learning and memory. The results revealed a pattern of deficits similar to that seen in clinical studies. In subsequent work, we produced evidence that CICI is more widespread than previously thought and that, despite some recovery, many effects are long lasting. On the treatment side, we found that donepezil, a drug commonly used to treat early stage Alzheimer's disease, and physical exercise, which is known to influence cognitive function in the elderly and brain-damaged populations, were both effective in reducing cognitive impairment caused by chemotherapy. The proposed research investigates different features of the relationship between chemotherapy and cognitive impairment. The following predictions will be tested: (1)CICI is related to impaired control of attention and thought processes; (2)reduced neurogenesis (production of new brain cells) and increased cytokine levels are biological mechanisms underlying CICI (3)age, stress, and life-style factors impact the severity of CICI; (4)tumour burden interacts with chemotherapy to exacerbate cognitive impairment; (5)CICI is best treated by a combination of drug and behavioural interventions.