A new study sheds light on “chemobrain”

After chemotherapy treatment, many patients say their mind has been affected. For example they describe symptoms such as feeling confused, memory problems and difficulty concentrating – a phenomenon that has been dubbed "chemobrain" (Cancer Research UK has more information).

The causes are little understood. Are these apparent neuropsychological effects due to a direct physical effect of chemotherapy on the brain? Or could it be the stress and worry involved in chemotherapy that is responsible? Perhaps it's both. To find out more, Mi Sook Jung at Chungnam National University in South Korea, and colleagues, conducted repeated brain scans and neuropsych tests with breast cancer patients undergoing chemo and compared them with similar cancer patients not on chemo and healthy controls. Reporting their results in Brain Imaging and Behaviour, the researchers hope a better understanding of the nature of "chemobrain" and its causes will make it possible for health professionals to offer patients better support and care.

The participants were 28 women who'd had surgery for breast cancer and were waiting to start chemo; 34 women with breast cancer of similar severity, also post-surgery, but awaiting radiotherapy without chemo; and 30 age-matched healthy controls (average age across groups was 52, and the women were predominantly white and well-educated).

On three occasions, all the participants completed tests of their verbal working memory while having their brains scanned. To provide a baseline, they completed their first tests before the chemo group had begun their chemotherapy treatment; the second test was at least one month after chemo; and the third and final test was 12 months after the baseline (and 7 months after chemotherapy for the chemo group). The women also reported their cancer symptoms, any cognitive complains and psychological stress.

The chemo patients performed worse at the memory task, and their lower performance became more obvious over the course of the year: whereas the other patients and healthy controls improved on each test (just as you'd expect with repeated practice), the chemo patients did not. Throughout, the chemotherapy patients' brain scans also showed some signs of a lack of neural efficiency at the front of their brains while they completed the memory tests, although this only reached statistical significance in comparison with the other groups at the final test.

In terms of subjective cognitive complaints (for example, how much the participants said they experience memory problems in everyday life), there were actually no group differences. In other words, if the researchers had relied on self-report, rather than conducting memory tests and brain scans, they wouldn't have found evidence for chemobrain as such. Across all the cancer patients, the greater their psychological distress and the more severe their cancer symptoms, the more that they tended to complain of cognitive problems.

Taken together, the researchers said there could be two distinct phenomena here: the subjective cognitive problems associated with cancer may be caused predominantly by anxiety and the burden of cancer symptoms; at the same time, chemotherapy may be having an additional, compounding effect on brain function, which showed up in the memory tests and brain scans.

Focusing on why chemotherapy treatment has these additional adverse effects, the researchers believe part of this is likely the anxiety and stress specifically involved in the chemotherapy experience, such as anticipation of hair loss and other toxic effects. Supporting this, the chemo patients actually showed some signs of altered brain function even before they'd started their chemotherapy.  However, having chemotherapy was still associated with greater risk of neural inefficiency, even after putting levels of psychological distress into the analysis, which points to a direct organic effect of chemotherapy on the brain, compounding the psychological toll (stronger evidence for a direct organic effect of chemotherapy on brain function, separate from psychological causes, would require a controlled experiment with some patients allocated to a "sham" chemotherapy condition, though this would surely be unethical).

This is a relatively small study with complex findings and much more research is clearly needed, including into how and why chemotherapy might directly effect brain function. The researchers said "considerable research is underway to identify biological mechanisms by which chemotherapy alters neural function (e.g., inflammatory cytokine production, genetic predisposition), [but that] research also is needed to explicate the mechanism linking symptom burden and self-reported cognitive problems."