Study Uncovers Mechanism Behind Cognitive Impairment in Chemotherapy Patients

While chemotherapy remains one of the most common types of cancer treatment, it can have a number of serious side effects, including cognitive impairments. Researchers at the University of Kansas have now identified the potential mechanism behind this side effect – commonly referred to as “chemo brain” – and may have even identified some new ways to treat and prevent it.

“[Chemo brain is] something doctors learned about because patients were complaining,” said Dr. Michael A. Johnson, associate professor in the department of chemistry at the University of Kansas. “Symptoms include visual and verbal memory loss, so if you have a conversation with somebody, you may have difficulty recalling it. You might have attention deficit, so if you are trying to do taxes, it might be difficult to focus. It also can result in a decline in processing speed, so it may be more difficult to think on your toes. You may have trouble remembering words.”

Johnson and his colleagues found that 5-Fluorouracil – a chemotherapy agent commonly used to treat cancers, including breast, colorectal and pancreatic – can have a damaging effect on the myelin sheath that protects nerve cells in the brain. The researchers noted that this myelin damage translated to neurodegenerative symptoms in an area of the brain responsible for learning and memory, known as the hippocampus.

The researchers also found that treatment with chemotherapy was associated with elevated levels of hydrogen peroxide in the brains of mice. When these animals were treated with an experimental compound known as KU-32, the negative effects of hydrogen peroxide and the cognitive decline associated with chemotherapy treatment were mitigated.

“In our preliminary results, we found that hydrogen peroxide temporarily increases in the brains of chemotherapy-treated rats,” said Johnson, whose paper was published in the journal, Behavioural Brain Research. “Because hydrogen peroxide is a reactive oxygen species and potentially damaging, it may have an effect on cognitive function.

“Additionally, we may have a therapy that can serve as a preventative in order to treat it. We found that KU-32 prevents cognitive impairment, and our preliminary neurochemical data suggest that it may prevent increases in hydrogen peroxide production.”

The results of this study could help physicians treat the symptoms of chemo brain in the future. More preclinical data on KU-32 will need to be collected before the drug can be tested in human patients.