People undergoing cancer treatment often report experiencing “chemo brain,” or states of confusion and cognitive impairment due to aggressive chemotherapy treatment. But new research suggests that these cognitive problems might start earlier, with the development of cancer tumors.

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Could ‘chemo brain’ be due to more than just chemotherapy? Researchers investigate.

Researchers at the Baycrest Centre for Geriatric Care in Toronto, Canada, conducted a study focusing on the “chemo brain” effect, with the purpose of understanding to what extent these states of cognitive impairment are caused by the treatment.

Lead author Dr. Gordon Winocur and his team conducted experiments in mice, which led them to observe that problems in learning and recall began to occur prior to chemotherapy in the animals with cancer.

“Our work,” explains Dr. Winocur, “isolated that the cancer is responsible for some of the memory and thinking complaints experienced by cancer survivors, and that drug therapy adds to the problem.”

He adds, “Both factors independently affect brain function in different ways, which can lead to the development of other psychological disturbances, such as anxiety and depression.”

The team’s findings were recently published in the journal Neuroscience.

Research covered by Medical News Today early this year indicated that chemo brain can severely impact people undergoing cancer treatment, with over 45 percent of breast cancer survivors reporting significantly impaired cognitive performance after chemotherapy.

In the current study, the researchers noted that female mouse models with breast cancer exhibited three distinct brain changes related to cognitive function, one of which was independent from exposure to chemotherapy.

First, they saw that the immune system reacts to the development of cancer tumors by releasing cytokines, which are a type of protein that play a key role in cell signaling. This is a natural response, with the aim of preventing the cancer from spreading further.

However, the study revealed that this immune system reaction also triggers inflammation of the nervous system, which affects normal brain functioning.

Secondly, they noticed that chemotherapy impaired neural regeneration in the hippocampus — the brain region largely responsibly for memory storage and recall — causing memory loss.

Finally, the development of cancer tumors alongside exposure to chemotherapy led to a decrease in frontal lobe and hippocampal volume. Both of these brain regions play a key role in memory formation and recall.

Our research found that the cancer and chemotherapy cause three separate, but related brain changes. Understanding the nature of the cognitive impairment and the underlying biological mechanisms are essential to the development of an effective treatment for chemo brain.”

Dr. Gordon Winocur

“Our work shows that a targeted approach addressing all three issues is necessary to successfully treat the condition,” he adds.

For the purpose of this study, the scientists conducted experiments on female mice, half of which had breast cancer. The other half, which were cancer-free, were used as controls.

At baseline, all of the mice underwent targeted tests measuring learning and memory capacity. This allowed Dr. Winocur and team to gauge how cognitive function was impacted by cancer and chemotherapy.

Then, both the groups received three weekly injections of either methotrexate and 5-fluorouracil — which are drugs commonly used in chemotherapy — or a saline solution. The researchers then took scans of the mice’s brains, as well as samples of blood and tissue, for analysis.

They found that the tumor-bearing mice exhibited reduced cognitive performance — compared with the control mice — even before exposure to the chemotherapy drugs, suggesting that memory and learning impairment actually begin with the development of cancer tumors.

Following the administration of chemotherapy drugs, cognitive function was impacted even further in tumor-bearing mice, and the healthy mice also exhibited memory and learning impairments.

“People are living longer thanks to more effective chemotherapy and cancer treatments,” says Dr. Winocur, which is why “[a]ddressing chemo brain will help improve a patient’s quality of life since these side effects can lead to emotional and mental health issues that affect a person’s ability to function in society.”

Further research, he explains, will focus on ways to counteract chemo brain more effectively, also taking into account the new findings that suggest that cancer itself plays an independent role in causing cognitive problems.

In older studies, Dr. Winocur and team found that drugs used to treat memory loss in Alzheimer’s disease, paired with a physical exercise regime, could lessen the chemo brain effect, so next, he and his colleagues are interested in pursuing this line of investigation.