Up to 70% of cancer survivors report changes in their cognition, particularly memory and concentration.  Studies that have formally tested neuropsychological function show that 20-30% of survivors have cognitive impairment prior to receiving any chemotherapy, and 20-50% have impairment after chemotherapy, although some studies reported no cognitive impairment and one reported decline in cognitive function in 61% of patients after chemotherapy.  The cognitive domains most affected are: processing speed, learning and memory and executive function.

Studies consistently show only a weak association between self-reported cognitive function and neuropsychological performance on formal cognitive testing.  Cognitive symptoms are strongly associated with fatigue, anxiety and depression, and impaired quality of life; but these symptoms are not correlated with neuropsychological impairment on cognitive testing.   

The underlying mechanisms of cognitive impairment in cancer survivors are unknown, but hypotheses include: direct neurotoxicity, release of cytokines, hormonal changes, blood clotting in small cerebral vessels, and genetic predisposition.

Neuroimaging studies of cancer survivors show that chemotherapy can cause structural and functional changes, with changes in white matter and reduction in total brain volume and grey matter seen 10-20 years after treatment.   The results of functional studies where patients are scanned while performing a cognitive task show changes in activation in some brain regions in cancer patients compared to healthy controls.  

Preclinical studies have shown that a number of chemotherapy agents, including methotrexate, 5-flurouracil, doxorubicin and paclitaxel, cause cognitive impairment in rodents.   Studies have shown that chemotherapy can damage multipotent neural progenitor cells.   The hippocampus and frontal systems seem to be most affected.  

Currently there are no proven interventions to prevent the cognitive impairment from occurring or to treat it once it has occurred, though preclinical studies are evaluating various pharmacological agents such as fluoxetine and anti-oxidants, and physical activity, and a number of studies are being conducted in cancer survivors to evaluate the efficacy of cognitive rehabilitation.