Long Term Effects of Chemotherapy on Cognition, Preventative Potential of Antidepressants

Each year, over 1.6 million people in the U.S. alone will be diagnosed with some form of cancer. With advances in treatment, survival rates have risen to nearly 65%. While remission and survival are the ultimate goals of treatment, it has become clear that many cancer survivors (estimates range from 15% to 70%) treated with chemotherapy experience significant, long-lasting cognitive impairment. This chemotherapy associated cognitive impairment is often called Chemo Fog or Chemo Brain. For some, the effects are mild, such as having difficulty with focusing, concentrating, and speed of processing. For others, the cognitive impairments can be significant and may dramatically alter their day-to-day lifestyles, even preventing some from ever returning to work. Growing evidence suggests these impairments are sometimes permanent. The present study attempts to identify the underlying mechanisms of Chemo Fog that contribute to impairment in learning, memory and processing speed, associated with chemotherapy administration. This study also investigates a potential antidepressant treatment that, when co-administered, may reduce the effects of chemotherapy drugs. Two proposed explanations as to why such changes follow chemotherapy treatment are; a reduction in the proliferation of new brain cells, and a decrease in the myelination of axons. A B6 strain of mice was used as a model for this investigation. Animals were administered the chemotherapy agent 5-Fluorouracil (5-FU) and five a known neuroprotectant (fluoxetine) over a period of 5 days. Neural tissue was examined to assess the effects of the treatment at 1 day, 14 days and 6 months post-treatment. A chi squared test was used to analyze data from day 1 and day 14 tissue. A Oneway Anova test was used to analyze data from 6-month tissue. Analysis revealed a significant reduction in myelin at 1 and 14 days but not 6 months for individuals that received only 5-FU as compared to controls. Analysis also showed that animals treated with fluoxetine and 5-FU had myelin that was consistent with control animals for short-term time points (1+14 days) suggesting myelin preservation. Statistical tests showed no myelin protection for the animals treated with fluoxetine at the 6-month time point as their tissue was not statistically different from animals receiving 5-FU alone