Recipients of the Award for Excellence in Quality of Life Research
Stephen R. Rapp, Ph.D.
Professor, Psychiatry and Behavioral Medicine
Wake Forest University Baptist Medical Center
2004 Award for Excellence In Quality of Life Research
Society for Neuro-Oncology Award supported by The Sontag Foundation
Merit Award: $2,000
About Dr. Rapp's Research:
Improving Cognitive Functioning in Brain Irradiated Patients: A Phase II Trial of an Acetylcholinesterase Inhibitor (Donepezil)
Patients who have undergone cranial radiation for primary or metastatic brain tumors often suffer neurocognitive effects that interfere with daily activities, mood, and quality of life (QOL). Donepezil (Aricept) is an acetylcholinesterase inhibitor that has been effective in improving cognitive functioning in patients with dementia. The study was designed to determine whether donepezil could also be useful for brain tumor patients who had undergone radiation. This study was an open-label, Phase II clinical trial of donepezil. Patients were recruited if they were >18 years of age had a life expectancy > 30 weeks, had completed partial or whole-brain irradiation of at least 3000 cGy >6 months prior to enrollment, had had no evidence of progressive brain disease for 3 months, were on a stable/decreasing steroid dose, had a Karnofsky score of >70, and had no planned brain tumor treatment therapy during study.
Each patient received 5 mg/day of donepezil for 6 weeks, which was increased to 10 mg/day for 18 weeks, followed by a 6-week wash-out period. Neurocognitive measures were taken at baseline, 6 weeks, 12 weeks, 24 weeks, and 30 weeks. Neurocognitive functions assessed (and measures) included global cognitive function (Mini Mental State Exam), verbal fluency (F-A-S), attention/concentration (Trail Making Test-Part A, Digit Span Test), verbal memory (California Verbal Learning Test-II), figural memory (modified Rey-Osterrieth Complex Figure), and executive function (Trail Making Test-Part B). Health-related QOL and mood were also assessed and are reported elsewhere.
All measures were administered and scored by a trained and certified research nurse. Changes in neurocognitive scores from pre-treatment baseline to week 24 are presented. Data from 24 (mean age = 43 years; female = 47%; white = 91%) of 34 enrolled patients who completed all assessments were analyzed.
Scores significantly improved between baseline and week 24 on verbal fluency, verbal memory, attention/concentration, and figural memory. There were no significant changes for global cognitive function, or executive function.
No significant worsening of performance was noted on any measures. A 24-week course of donepezil was associated with improved performance in several important cognitive functions in middle-aged adults. Donepezil may be useful in reducing the adverse late effects of partial or whole-brain irradiation and improve cognitive function of patients. Research was supported by NCI grants 1 U10 CA 85851.
