Temporary Brain Shrinkage May Explain 'Chemobrain'

CHIBA, Japan, Nov. 27 -- The thought-fogging phenomenon known as "chemobrain" appears to be related to a reversible shrinking of brain structures induced by chemotherapy, researchers here have found.

MRI scans of breast cancer survivors within a year of completing adjuvant chemotherapy showed significantly smaller regional volumes of gray and white matter in areas involved in cognitive function compared with other survivors or healthy controls, they reported in an online release from the Jan. 1 issue of Cancer.

By three years after treatment, however, those differences had vanished, said Masatoshi Inagaki, M.D., Ph.D., of the National Cancer Center Hospital East, and colleagues.

"Results lead to the idea that adjuvant chemotherapy could have a temporary effect on brain structure," the authors wrote. "These findings can provide new insights for future research to improve the quality of life of cancer patients who receive adjuvant chemotherapy."

Patients undergoing chemotherapy often complain of cognitive and memory problems, and clinical studies have confirmed cognitive declines. Evidence from animal studies has also shown that systemic chemotherapy can have neurotoxic effects.

"Chemotherapeutic agents are hypothesized to have neurotoxic potential through their ability to interfere with DNA and RNA synthesis and function, inhibition of microtubule formation, and/or immunosuppressive properties," the investigators wrote.

They performed a retrospective study to determine whether there were significant regional brain-volume differences between breast cancer survivors exposed to adjuvant chemotherapy and those who did not undergo chemotherapy.

The authors compared gray and white matter volumes as measured on high-resolution 1.5-tesla brain MRI scans from databases of breast cancer survivors, both in breast cancer patients who were within one year of their surgery, and those who were three years out from surgery. They also compared data on cancer survivors with scans taken from healthy controls recruited from the local population for the study.

They found that in the one-year study survivors who underwent chemotherapy had smaller gray matter and white matter in areas involving cognition and memory, including the prefrontal, parahippocampal, and cingulate gyrus, and precuneus regions, compared with patients who were not exposed to chemotherapy.

When they looked at the three-year data, however, they saw no differences between the patients who had received adjuvant chemotherapy and those who had not.

The authors also performed an analysis to determine whether the volume of key brain structures correlated with scores on the Weschler Memory Scale-Revised, and found that the volumes of the prefrontal, parahippocampal gyrus, and precuneus regions were significantly correlated with indices of attention and concentration and/or visual memory.

When they compared the brain regions of all cancer survivors at the one- and three-year intervals with those of healthy controls, however, they did not see any significant differences, suggesting that there were no significant effects of the cancer itself on cognitive function.

The authors noted that the effects of chemotherapy on specific brain regions were unclear, and that the potential pathophysiologic mechanisms for the differences they saw in regional brain volumes were unknown.

They also noted that "the reason we did not explore effects of each chemotherapeutic agent in the study setting was that interactions between each chemotherapeutic agent may exist and may make our inference difficult."

They also pointed out that the current study did not have any specific functional targets related to each of the detected regions.

Nonetheless, "these results indicate a potential effect of adjuvant chemotherapy on brain structure, and the change of the brain structure may be associated with memory function," they wrote.