Chemo brain or cancer brain?
From an article I received today:-
Chemo Brain Caused by More Than Just Chemo
Most people who have gone through chemotherapy are familiar with the term ‘chemo brain.’
The idea is that the chemotherapeutic drugs, designed to attack and destroy the cancerous tumors, also have negative effects on the brain. The ability to think clearly declines. Learning new material becomes harder and remembering past memories becomes more difficult. Some people have also reported completely losing train of thought in the middle of a sentence.
Chemo brain can even impact your mood. Chemo brain, also called post-chemotherapy cognitive impairment, can present in many different forms.
But what if the culprit is not entirely the chemo drugs?
Dr. Gordon Winocur, from the Baycrest Centre for Geriatric Care in Toronto, Canada, used mice to examine chemo brain. And what they found was that some of the cognitive impairment and memory decline began even before chemotherapeutic drugs entered the picture.
Breast cancer and chemo brain
Approximately twenty five percent of all cancer survivors report the trouble thinking and remembering that heralds chemo brain, but that number is almost double for breast cancer survivors at forty-five percent.
Other reproductive cancers also have higher rates of chemo brain than non-reproductive cancers. For most people, it goes away shortly after chemotherapy has ended. For others, it lasts a lot longer, potentially up to four years.
Living that long with impaired thinking and memory can have a serious impact on a cancer survivor’s quality of life. As Dr. Winocur said, “...these side effects can lead to emotional and mental health issues that affect a person’s ability to function in society.”
“People are living longer thanks to more effective chemotherapy and cancer treatments,” said Dr. Winocur. This longer lifespan is a good thing, but chemo brain can take the joy out of surviving.
Something had to be done to reduce the harm caused by chemo brain, and Dr. Winocur took up the job. It was while he was investigating the mechanisms behind this chemo brain when he realized that the cognitive decline started prior to the drugs. Obviously, this avenue needed to be researched.
Of Mice and Memory
Dr. Gordon Winocur’s team included Hal Berman, Mary Nguyen, Malcolm A. Binns, Mark Henkelman, Matthijs van Eade, Micheline Piquette-Miller, Melanie J. Sekeres, J. Martin Wojtowicz, Johnson, Yu, Haibo Zhang, and Ian F. Tannock.
Their work was published as Neurobiological Mechanisms of Chemotherapy-induced Cognitive Impairment in a Transgenic Model of Breast Cancer in the scientific journal Neuroscience.
The transgenic part of the title refers to the fact that they used mice, specifically FVB/N-Tg (MMTV-neu) 202 Mul/J mice, that had been genetically modified to develop breast cancer at a high rate. Often, cancer and tumors are different between species, but this type of mouse cancer is similar to human breast cancer.
One half of the mice used had breast cancer while the other half did not. The second half without brain cancer was used as the control group.
All of the mice were tested for their ability to learn and recall information. Brain scans and tissue samples were taken as well, to measure neurogenesis, brain volume, and inflammation caused by cytokines.
Then they gave three weekly injections to some of the mice--both experimental and control groups--with chemotherapeutic drugs, specifically methotrexate and 5-fluorouracil. The other mice received a saline solution injection, of the same amount of liquid, instead.
Chemotherapy magnifies pre-existing problems
“Our work 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,” said Dr. Winocur.
The cognitive decline began in the mice with breast cancer before the first chemo drug was injected. The learning and memory impairment was worsened by the drugs, and in the mice without tumors, the drugs initiated a decline in cognition.
By the end of the trial, the mice with both breast cancer and anti-cancer drugs had the worst ability to learn new or recall old information.
This change in brain function can lead to depression
He continued, “Both factors independently affect brain function in different ways, which can lead to the development of other psychological disturbances, such as anxiety and depression.”
Thankfully this was not just an observation. The tissue sampling and brain scans the research team performed allowed them to see just what was happening in the mice’s biology.
Cancer and chemotherapy cause separate but related brain changes
“Our research found that the cancer and chemotherapy cause three separate, but related brain changes,” said Dr. Winocur.
The first change to the brain involved the cytokines. Cytokines are proteins that your body uses as signaling agents and are an important part of the autoimmune response.
However, their role is often to cause inflammation, which is detrimental when it goes out of control. Such as the dysregulation that occurs when your body’s immune system is trying to respond to a cancerous tumor.
In fact, the cytokines released in response to the breast cancer even caused inflammation of the nervous system. An inflamed nervous system makes it harder for your brain to function properly.
Secondly, the cancer somehow impaired neural regeneration in the hippocampus. Since the hippocampus is the part of the brain mostly responsible for storing and recalling memories, this impairment lead to memory loss.
Thirdly, the cancer tumors also had an effect on the volume of the brain, especially the hippocampus and frontal lobes. This change in volume had a detrimental effect on the mice’s ability to think and learn.
That was all before the chemo drugs were injected. The methotrexate and 5-fluorouracil combination made all of the problems worse.
These results could change chemotherapy in the future
Learning that the cancer tumors affected the body in these three ways may lead to chemotherapy that effectively addresses chemo brain as well as the cancer.
“Understanding the nature of the cognitive impairment and the underlying biological mechanisms are essential to the development of an effective treatment for chemo brain,” said Dr. Winocur.
He continued, “Our work shows that a targeted approach addressing all three issues is necessary to successfully treat the condition.”
However, this is research that has yet to be conducted. While one of the three issues, the cytokine-caused inflammation, can be fought using anti-inflammatories, the other mechanisms will need more research before some counter method can be found.
Research think physical exercise can help drastically
The knowledge that the cancer tumor itself contributes to chemo brain will help other researchers better aim their efforts at combating chemo brain.
Dr. Winocur himself has an idea of where to start helping people, however. In some previous research he conducted on chemo brain, he found that combining physical exercise with drugs used to treat memory loss caused by Alzheimer’s disease was effective in reducing the effect of chemo brain.
He and his colleagues plan on following up with that information for their next project.
The underlying biology is still poorly understoof
Breast cancer survivors can have a hard time adapting to a post-cancer life, and chemo brain can make this even more difficult. This hardship takes its tolls on the survivors.
Researchers are trying to find ways to prevent or lessen the effects of chemo brain, but the underlying biological mechanisms are still poorly understood. Dr. Winocur and his team of researchers, while examining the topic, found that it’s not just ‘chemo’ brain, but that the cancer itself has an effect as well.
This will lead to more effective treatments for chemo brain in the future.
References
https://www.medicalnewstoday.com/articles/320139.php
https://www.sciencedirect.com/science/article/abs/pii/S0306452217307856
http://ascopubs.org/doi/full/10.1200/JCO.2016.68.5826
This is the link to the actual document (with ads)
