LAUSR

Cognitive impairment is frequently found in brain tumor patients. More than 90% of patients with brain tumor have at least one cognitive domain disturbance. Decline in cognitive function could happen before due to the tumor or after the treatment because of surgery, radiotherapy or chemotherapy. Until now there is no available standard treatment for patients with cognitive impairment due to brain tumor. Moreover, Donepezil is an acetylcholinesterase inhibitor known to be useful for improving cognitive function in patients with dementia. This clinical study aims to determine the cognitive effects of donepezil therapy in patients with brain tumors following surgery. This is a pilot study with total of 20 adult brain tumor patients were double blinded randomly assigned to receive a single daily dose (5mg for 12 weeks) of donepezil or placebo. The inclusion criteria were patients with primary brain tumor who had undergone surgery with cognitive impairment at the initial evaluation and age range 18 to 65 years old. Patients with previous cognitive problem, other diseases that can cause cognitive decline e.g. stroke and history of taking donepezil, memantine, methylphenidate, ginkgo biloba, and modafinil were excluded. A cognitive test using Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment Indonesia Version (MoCA-INA) assessing memory, attention, language, visuospatial, verbal fluency, and executive functions were administered before random assignment and at 4, 8 and 12 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Furthermore, side effects and adverse events were also recorded. Of this mostly middle-age (30–60 years old), female, meningioma as primary brain tumor with frontal and temporal lobe are the most frequent locations. After 12 weeks of treatment, the composite scores did differ significantly between groups (MMSE P=0.027, MoCA-INA P=0.024). Furthermore, the significant differences favouring donepezil were observed for orientation and recall domains using MMSE with p value 0.017 and 0.006 respectively. Visuospatial (P=0.034) and delayed recall domains (P=0.004) were significant through MoCA-INA evaluation. In addition, Mean MMSE score for pre-donepezil administration was 14.60 ± 4.47 and after 3 months was 20.40 ± 4.24 (P=0.000). Mean MoCA-INA score for pre-donepezil administration was 9.30 ± 3.65 and after 3 months was 15.30 ± 4.24 (P=0.000). However, there was no differences in the placebo group (MMSE P= 0.066, MoCA-INA P=0.313). Three months treatment with donepezil significantly improve the cognitive functions among post-operative brain tumor patients with no reported side effect. Moreover, further research is needed for longer duration of follow-up and possibility of increased doses.