Each year more than 215,000 Americans receive partial or whole brain irradiation for brain cancers. Radiation may cure or slow the cancer, but more than 50 percent of the patients who survive beyond six months experience cognitive problems, including poor short term memory, language difficulties, and confusion. Ten percent of all patients treated with radiation develop progressive dementia. Now, Edward Shaw and colleagues at Wake Forest University Medical School report that donepezil, a drug already approved for the treatment of Alzheimer’s disease (AD) patients, reduces post-irradiation difficulties.
In the small trial, 35 patients previously treated with radiation for primary brain cancer took donepezil for 18 weeks. The patients underwent cognitive testing prior to starting therapy as well as during and after treatment. Of the 24 individuals who completed the study, concentration and short-term memory improved significantly over baseline, and the researchers saw a trend toward improvement in verbal fluency. “The results were incredible,” Shaw says.
After a six-week period without taking the drug, the patients’ test scores had dropped again, indicating that the drug itself increased cognitive performance. Nearly half of the patients have opted to restart the therapy following the end of the trial.
The team is planning a large, randomized, controlled trial to confirm the results, which were published in the March 20, 2006, issue of the Journal of Clinical Oncology. In the meantime, because the drug increases neurotransmitter release by neurons, the data suggest that the neurons surrounding the treated area had been damaged by radiation. That finding is contrary to the current model of radiation damage, which suggests that blood vessels and support cells are damaged, but the neurons themselves are not. Future studies will focus on just what happens to neurons and support cells in the brain.