‘Chemo brain’ cognitive issues linked to poor lymphatic-system drainage

Cancer is a challenging enough diagnosis, but many patients are dealt a second blow, even as they heal: “chemo brain.”

Also called “brain fog,” this mix of cognitive issues—memory problems, struggling to find words, an inability to concentrate—affects up to three-in-four cancer patients, according to multiple studies. For many, the effects last years beyond cancer treatment.

A new study offers new models for studying causes of chemo brain and points to the effects of chemotherapy drugs on the brain’s lymphatic system, which is a network of tiny vessels in the brain’s protective membranes that help remove waste and transport immune cells. The study was published Oct. 13 in Communications Biology.

“There’s compounding evidence now that these meningeal lymphatics are involved in cognitive issues, including Alzheimer’s disease and traumatic brain injury, too,” said co-corresponding author Jennifer Munson, professor and director of the Fralin Biomedical Research Institute at VTC’s Cancer Research Center in Roanoke. “Women are affected by chemo brain, or brain fog, much more than men when treated by very common chemotherapies, such as those used on breast cancer patients on a regular basis.”

The study highlights considerations for cancer treatment beyond eradicating the cancer itself, said Monet Roberts, an assistant professor of biomedical engineering and co-corresponding author on the paper.

“Our study is important because it explores a very real, hidden layer of chemotherapy treatment that leaves lasting scars on the daily lives of those who are living with or have survived in their cancer journey,” said Roberts, a former postdoctoral associate who trained in Munson’s lab at the Fralin Biomedical Research Institute and now continues to study the lymphatic system in her own lab.

Munson and her team developed a three-tiered modeling system, using a combination of mouse and tissue-engineered models, to study changes to the lymphatic system. The in vitro model is the first human tissue engineered system that replicates this unique tissue, and has the potential for therapeutic testing, patient specific analyses, and disease-specific incorporation.

The study examined effects of two of the most common chemotherapy drugs, docetaxel and carboplatin. While both showed lymphatic system impacts, they were much more pronounced with docetaxel.

“What we see is a shrinking of the lymphatic vessels, and fewer loops or branches in the vessels,” said Munson, who is also a professor in Virginia Tech’s Department of Biomedical Engineering and Mechanics. “These are signs of reduced growth that indicate the lymphatics are changing, or not regenerating in beneficial ways. Lymphatic health really declined across all three models measured in different ways.”

As anticipated, brain imaging showed reduced drainage of the lymphatic system in mice. When the research team performed cognitive tests, they found that if a mouse had been treated with docetaxel, it exhibited poor memory.

Taken together, Munson said, the results suggest chemo brain could result from poor lymphatic-system drainage in response to chemotherapy.

“That could potentially account for some of these memory deficits, which is similar to what we have seen in Alzheimer’s disease,” Munson said.

“The first step is knowing,” she said. “And now the hope is to figure out how to help. Could delivering something pharmaceutically, such as a protein, alleviate the problem and not interfere with the chemotherapy? We know of other things that affect flow in the brain, as well, such as better sleep and exercise.”

Munson is also interested in exploring gender differences in chemo brain prevalence.

“Lymphatic diseases in general affect women more than men,” she said. “We are extremely interested in trying to understand that difference and why that difference might exist.”

“Ultimately, this work underscores the need to consider not only survival, but also the long-term, often overlooked neurological side effects of cancer treatment on cognitive well-being and quality of life,” Roberts said, “Especially in women who are disproportionately affected by these lasting side effects.”