It’s not unusual for cancer survivors to report problems with memory, attention, learning, and processing of information months or even years after completing treatment. Scientists are just beginning to understand why some people are particularly susceptible to these cognitive difficulties, which patients often call chemobrain or chemofog. New findings from two related NCI-funded studies—a clinical study in older women and a mouse study—may help shed further light on genetic risk factors for developing cancer-related cognitive problems. The clinical study results point to the role of the E4 version (or E4 allele) of the APOE gene, which is a risk factor for late-onset Alzheimer’s disease. In the study, published October 3 in the Journal of Clinical Oncology, older women with breast cancer who were treated with chemotherapy and were carriers of the E4 allele were more likely to have cognitive problems Exit Disclaimerthan women without cancer who were also carriers of the E4 allele. The results also suggest, but do not definitively prove, that older women with breast cancer who carried the E4 allele were more likely to have cognitive problems after chemotherapy than women without the allele or those receiving only hormonal therapy. In the second study, researchers described the development of an APOE mouse model of cancer-related cognitive problems. The study showed that the mice developed chemotherapy-related changes in spatial learning and memory as well as physical changes in brain regions involved in those functions. Learning and memory problems are commonly reported in human studies of cancer-related cognitive decline and Alzheimer’s disease. The mouse study was published October 4 in Neurotoxicity Research. Although other studies have shown evidence of a link between the E4 allele of APOE and cognitive problems after chemotherapy in cancer survivors, “our study is the only large study to investigate this link in older cancer patients,” said Jeanne Mandelblatt, M.D., M.P.H., a geriatrician at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC) and lead author of the clinical study. William Rebeck, Ph.D., a neuroscientist at GUMC, led the mouse study, which he did in collaboration with Dr. Mandelblatt and other GUMC colleagues. “These results are very exciting for furthering our understanding of who may be susceptible to cancer-related cognitive problems and may provide insight into some of the mechanisms involved,” said Michelle Janelsins, Ph.D., M.P.H., of the University of Rochester’s Wilmot Cancer Institute, who studies cancer-related cognitive difficulties but was not involved with the two new studies. However, before these results can be used to inform clinical practice, the research findings from this genetic study need to be confirmed with additional studies with a larger number of patients who have the E4 allele and receive chemotherapy, Dr. Janelsins said. The E4 allele of APOE is only present in about 25% of the US population, and fewer than 30% of older women receive chemotherapy for their breast cancers, explained Dr. Mandelblatt.