Some Older Breast Cancer Survivors With Alzheimer's Gene Experience Chemo Brain

Chemo brain. Mental fog. Cognitive decline. No matter which it’s called, all refer to the thinking and memory problems often experienced by patients after cancer treatment.

Researchers are still trying to understand what causes it to occur and studies suggest it isn’t just from chemotherapy alone. The Thinking and Living with Cancer (TLC) study, which was funded by the National Cancer Institute, dove further into investigating these cognitive changes, showing a potential link in older patients to a gene associated with Alzheimer's disease risk.

“It is well established that patients can experience cognitive problems after cancer diagnosis and treatment,” said study author Jeanne Mandelblatt, M.D., M.P.H., professor of oncology at Georgetown Lombardi Comprehensive Cancer Center, in Washington, D.C. “It’s not always solely experienced after chemotherapy. It’s now recognized that this is a clear cancer-related effect and it’s referred to more broadly as cancer-related cognitive decline.”

Mandelblatt and a team of researchers from six centers across the United States examined the effects in breast cancer survivors between the ages of 60 to 98 years. Participants were recruited between August 2010 and December 2015.

Researchers compared 344 women who had received a diagnosis of primary non-metastatic breast cancer with 347 women without cancer. Twenty-seven percent of survivors received chemotherapy (with or without hormonal therapy), and most of the chemotherapy regimens were anthracycline-based.

Cognitive function was measured in two ways: a survey of how the women felt they were thinking and neuropsychological tests. The 13 neuropsychological tests examined attention, processing speed, executive function (ability to organize different things), learning and memory. The women were tested before treatment, and then at the one- and two-year mark. They were also tested for the APOE gene, which directs proteins involved in normal lipid (fat) metabolism. However, one of the three types of the gene — APOE e4 — also has been found to predispose individuals to Alzheimer’s, according to Mandelblatt. “This is the strongest genetic risk for Alzheimer’s disease,” she said.

Researchers found that over the two-year period on average, women without cancer did not show any cognitive problems, regardless of genotype. Women treated with hormone therapy suffered limited cognitive problems, and this was mainly seen in women who carried the APOE e4 gene. But survivors with the APOE e4 gene who received chemotherapy (with or without hormonal therapy) experienced a noticeable decline.

“If a person needs treatment, their primary concern is to survive cancer,” said Mandelblatt. “If we understood which types of treatment and who was susceptible it might factor in to treatment decisions.”

However, she noted that the declines seen were small in magnitude and more research is needed. “We are looking at the data to see how that degree of cognitive change translates to daily function,” said Mandelblatt. “We speculate that there are some common pathways involved in both aging, cancer-related cognitive decline and neurodegenerative diseases.”

Because this study is ongoing, the researchers will follow up again with survivors at five years. Some have agreed to undergo MRI-imaging of the brain, which may help researchers in understanding some of the mechanisms.

Mandelblatt encouraged patients to talk with their doctors who will be able to help them overcome some of the cognitive concerns. Cognitive training therapy; physical activity, such as yoga; or word games may improve cognitive function after cancer and its treatments. Eating vegetables, getting enough sleep, keeping a planner and following routines are additional tips in helping to fight memory issues, according to the American Cancer Society. Until more information is available, routine testing for APOE subtypes is not recommended for making decisions, and all individuals should practice “cognitive-friendly” lifestyles.

“This is one of many important long-terms effects of cancer treatment that women should be aware of,” said Mandelblatt. “And it should be included in their survivorship care.”