Alzheimer’s drug improves cognitive function after RT for brain tumors

The study by Rapp et al. suggests that for brain tumor survivors experiencing cognitive difficulties, intervention with donepezil, a drug approved for use in Alzheimer’s disease (AD), may be helpful. Although average improvements were small, the trial indicates clear benefit for some patients, especially those most impaired. The study followed patients taking the drug for 6 months, but patients who responded to treatment likely will continue with lifelong therapy, based on experience with donepezil in AD. After cessation of the agent, neurocognitive function of treated AD patients declined to the level of untreated patients.

The results of the current study justify administering the drug to affected patients and monitoring for effects. In the absence of evidence of clinical benefit, the data do not support continuing treatment. Donepezil use in AD is continued for some patients even without signs of improvement, on the basis of slowing expected decline. However, cognitive declines due to tumor and treatment injury do not progress over time, and donepezil use in this population is supported only with evidence of benefit.

Optimal dosing for cancer patients requires further study, but studies with AD patients showed no clear benefit of dose escalation that outweighed GI adverse effects.

Maintaining maximal cognitive functioning in patients who often begin treatment with brain injury due to the tumor and unrelated illnesses, requires first the prevention of further damage. Strategies include functional image-guided surgery, limiting daily radiation fraction size, improved image-guided radiotherapy target definition, highly conformal radiotherapy administration techniques, and highly focused stereotactic radiosurgery in place of whole-brain radiotherapy for many patients with brain metastasis. Research on improvements in imaging of tumor and functional brain to better guide surgery and radiation is worthwhile.

Neurocognitive rehabilitation is recommended for patients with cognitive deficits that persist after therapy had ended. A recent randomized study showed clear benefit of rehabilitation for attention, verbal memory, and mental fatigue.

By taking steps to prevent injury, rehabilitate patients with deficits, and administer drug therapies while monitoring for benefit, improvements to cognitive function in brain tumor survivors may begin to increase. To best employ these strategies, a validated, easy-to-use instrument that measures mild to moderate impairment is needed for routine oncology practice.

Dr. Lawrence Kleinberg is associate professor of radiation oncology and molecular radiation sciences at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore. These comments were excerpted from the editorial accompanying the report by Dr. Rapp et al. (J. Clin. Oncol. 2015 April 20 [doi: 10.1200/JCO.2014.60.2805]).