A new study investigating the effects of chemotherapy on cognitive function in mice has confirmed what many cancer patients receiving treatment have often complained about – a decline in their memory and other cognitive functions, sometimes characterized as “chemobrain”.

The study, led by Dr. Gordon Winocur of the Baycrest Research Centre for Aging and the Brain, in collaboration with Drs. Ian Tannock and Janette Vardy of Princess Margaret Hospital, was conducted at Trent University. The findings are published in the September 2006 issue of Pharmacology, Biochemistry and Behavior (Vol. 85, Issue 1), which will be available online in the next week. The results were presented at a workshop held in conjunction with the 8th World Congress of Psycho-Oncology in Venice last week.

“In our study, we identified learning and memory deficits in the mild to moderate range in the drug-treated mice compared to the controls,” says Dr. Winocur.

“That the deficits were relatively small is encouraging. It’s important that cancer patients continue with these drugs and know that if they experience mild to moderate impairments in their cognitive functions, this level of change is potentially manageable.”

While there is growing evidence from studies of cancer patients on chemotherapy that the chemobrain effect does exist, many of the studies have suffered from methodological limitations. These include small samples, less than adequate controls and failure to account for other factors, including disease-related complications and stress, which could affect performance.

This latest study, using an animal model, afforded researchers the opportunity to look at the direct effects of chemotherapy drugs on cognitive performance without interference from potentially confounding variables.

In the study, 25 healthy female mice were split into two groups: the drug treatment group received standard doses of methotrexate and 5-fluorouracil (5FU), two drugs widely used in women to prevent recurrence of breast cancer; and the control group received a saline solution. Both groups were given their treatments over three weeks.

One week after the final injection they were put through a series of spatial/non-spatial memory tests and conditional rule learning tests in a water maze. The behavioral tasks enabled investigators to assess various aspects of learning and memory associated with different brain regions. The drug treatment group scored lower on the spatial memory task (hippocampus) and the task requiring strategic and working memory components (frontal lobes), especially when there were long delay intervals, compared to the control group. The drug group was not impaired on a cued memory test or in discrimination learning, tasks that are not affected by selective damage to the frontal lobes or hippocampus.

“This indicates that the adverse effects of this treatment regimen of methotrexate and 5FU probably do not extend to all regions of the brain. It appears that the hippocampus and frontal lobes are primarily affected,” says Dr. Winocur.

Because the behavioral testing was initiated two weeks after the last treatment and completed within four to five weeks, the study assessed only the short-term effects of the drugs. This is important because it raises the possibility that at longer treatment intervals there might have been some recovery of cognitive function, notes Dr. Winocur.

The research was supported by a grant from Science and Engineering Research Canada, and a Young Investigator Award from the American Society of Clinical Oncology.