Abstracts

It is well established that individuals with epilepsy frequently report memory problems and show deficits on objective memory measures. In recent years, cholinesterase inhibitors such as donepezil have been shown to improve memory or delay memory decline in patients with other neurological disorders (e.g., dementia, multiple sclerosis). The purpose of this double-blind, placebo-controlled, cross-over study was to determine whether donepezil would improve memory or other cognitive functions in epilepsy patients. Twenty-three epilepsy patients with subjective memory complaints (9 simple partial, 14 complex partial or generalized; mean age: 41 SD =9.25; 16 males, 7 females) were tested at baseline, after 3 months on donepezil, and after 3 months on placebo. Patients were randomized into two treatment groups receiving 3 months of donepezil followed by 3 months of a placebo, or vice versa. Donepezil was started at a dose of 5mg/day for 4 weeks and increased to 10mg/day for the remaining 8 weeks. Functions tested included verbal memory (Hopkins Verbal Learning Test, Medical College of Georgia ([ldquo]MCG[rdquo]) story memory), visual memory (MCG Figure Memory Test), Attention (Continuous Attention Test, Stroop Test), visuomotor speed (Symbol Digit Coding), and fine motor speed and dexterity (Grooved Pegboard). Subjective memory complaints, quality of life and mood were assessed with the QOLIE-31 and Profile of Mood Scale (POMS). Change scores were calculated comparing baseline with both placebo and donepezil, and these difference scores were compared via paired sample t-tests. While on donepezil, patients exhibited significantly stronger performance on MCG immediate story recall (donepezil mean change: 11.08 (SD=11.69), placebo mean change: 6.78 (SD=10.99), p=.04). However, they also showed poorer Stroop performance (p=.02), reported lower energy and [ldquo]vigor[rdquo] (p=.01), and indicated poorer [ldquo]quality of life[rdquo] (p=.01) on donepezil compared to placebo. Across donepezil and placebo treatment periods, there were no significant changes in subjective memory report or in number of side effects reported while patients were on donepezil versus placebo . There were also no significant differences in seizure frequency (p=.55). No patient reported any adverse event. Although patients exhibited improvement in immediate memory while on donepezil, they also exhibited worsening in attention, energy and quality of life. These results suggest that donepezil does not provide significant benefit for patients with epilepsy and subjective memory impairment, though this does not rule out possible benefit in individuals. There was no effect on seizure frequency in this study. (Supported by Pfizer Inc.)