Chemo Brain: A Decade of Evidence

Jeffrey S. Wefel, PhD; Alice Goodman, MA

Disclosures

November 01, 2013

In This Article

3 Lines of Evidence Converge

Medscape: What is the evidence that chemo brain is associated with chemotherapy?

Dr. Wefel: A decade of global research supports the concept of chemo brain, with the vast majority of studies occurring in breast cancer patients. Our group published a seminal longitudinal neuropsychological study in 2004, demonstrating decreased memory, executive function, and processing speed associated with chemotherapy in women with breast cancer.[1] Since then, other longitudinal studies initiated around the globe have demonstrated cognitive decline in a subset of breast cancer patients treated with chemotherapy.[2,3,4]

We know that many chemotherapies used to treat breast cancer are associated with cognitive changes; such agents include 5-fluorouracil, adriamycin, cyclophosphamide, and methotrexate. Hormonal agents, such as selective estrogen-receptor modulators (eg, tamoxifen) and aromatase inhibitors, have also been associated with cognitive changes.

Imaging studies have shown changes in brain structure (gray-matter density and white-matter integrity), as well as changes in brain function during the resting state and in task-based activities, both acutely after completing chemotherapy and long after primary treatment has been completed.[5,6]

Finally, a growing body of preclinical research using in vitro cell lines and animal models has elucidated some of the neurobiological mechanisms underlying this neurotoxicity. These studies have demonstrated that some chemotherapies affect cell populations involved in cognition (ie, neural progenitor cell populations and mature oligodendrocytes).[7,8] These models also are paving the way for the exploration of biologically based interventions that may prevent or ameliorate cognitive dysfunction in cancer survivors.

These 3 lines of converging evidence provide support for what patients have been telling us for years about their cognitive changes after chemotherapy.

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